家猪I型干扰素多基因家族的结构和特性及干扰素-alpha对口蹄疫基因工程疫苗的免疫增强作用
|
摘要
第一章:猪干扰素-alpha多基因家族的结构和性质研究
家猪基因组测序计划(Swine Genome Sequencing Project)提供的序列数据使得我们能够对猪IFN-α多基因家族的性质进行系统的分析。通过BLAST的方法,我们从已提交的序列工作草图中获得了16条IFN-α亚型的基因序列(Porcine interferon-α,PoIFN-α),其中包括14条功能基因和2条假基因。多序列比对发现,有6条功能基因编码的蛋白在C端出现了8个氨基酸的缺失。构建的PoIFN-α多基因家族系统发生树揭示各亚型之间的进化关系。除此以外,对PoIFN-α蛋白分子C端的进化速率分析和阳性选择分析说明C末端的缺失不是某些亚型向假基因进化的标志,而是在基因组中保持进化优势的一种策略。为了进一步分析PoIFN-α家族的性质,从猪的肝脏基因组中分离出了8种不同的PoIFN-α亚型基因,然后将这些基因克隆入真核表达载体中,筛选阳性克隆后重组质粒转染BHK-21细胞并表达48小时收集上清液。转染效率通过荧光定量RT-PCR标定,使其保持一致。分别利用WISH细胞/VSV病毒和PK-15细胞/PRV病毒两种干扰素检测系统测定细胞转染上清液中的抗病毒活性。实验结果表明完整的PoIFN-α亚型的抗病毒活性在WISH细胞中比C端缺失的亚型高2-50倍,在PK-15细胞中比C端缺失的亚型高15-55倍。但是没有发现尾部的缺失对PoIFN-α的酸稳定性产生影响。为了进一步分析PoIFN-α各亚型在不同病毒诱导条件下的表达情况,我们采用了两种PCR检测策略:对每种亚型设计特异性引物检测和设计PoIFN-α通用引物检测。实验结果表明,在Poly IC-DEAE-dextran诱导的PK15细胞中,PoIFN-α2、-α3、-α4、-α8、-α9五种亚型在诱导6hr/24hr后得到了表达;在PRV感染的PK15细胞中,PoIFN-α2、-α3、-α8、-α9、-α10、-α13六种亚型的表达出现上调;在SFV弱毒株感染的PK15细胞中PoIFN-α2、-α3、-α4、-α8、-α9、-α10六种亚型在诱导后得到表达。荧光定量PCR分析的结果表明,Poly IC-DEAE-dextran和PRV诱导的PK15细胞中PoIFN-α的表达上调存在时间依赖性,而SFV弱毒株感染的PK15细胞中PoIFN-α的表达在6hr和24hr没有明显的不同。
第二章:干扰素-θ,一种哺乳动物新型干扰素基因家族性质的研究
通过对家猪基因组测序计划提交的工作草图序列进行生物信息学分析,我们发现了一组干扰素基因近似序列。该组基因编码的蛋白质与其他I型干扰素存在23%-59%的氨基酸序列同源性,SMART软件预测发现其具有I型干扰素的保守结构域,同时进化分析表明该基因家族与小鼠的IFN-ζ基因及家猪的IFN-δ具有较近的系统发生关系,综合以上几点我们认为该组基因是一个新型的I型干扰素基因家族,命名为IFN-θ。IFN-θ基因家族由8个亚型组成,其中有5个亚型编码具有生物功能的蛋白质,而其他3个亚型为假基因。在5个功能亚型中,IFN-θ2与IFN-θ3、IFN-θ4与IFN-θ5分别具有很高的序列同源性,而IFN-θ1与其他4个亚型均有80%左右同源性。我们根据基因组分析得到的序列设计引物并以家猪肝脏基因组DNA为模板,利用PCR的方法分离到了5条IFN-θ功能基因。将IFN-θ的三种亚型(IFN-θ1、IFN-θ2、IFN-θ5)克隆入真核表达载体并转染细胞,经过48小时表达后收集上清液,生物活性分析表明IFN-θ的三种亚型在PK-15细胞和IBRS-2细胞中均有抗病毒功能,但是三个亚型的抗病毒活性明显不同。在病毒诱导表达谱分析中,PRV、SFV减毒株及Poly IC均能够在不同时间点在IBRS-2细胞中诱导IFN-θmRNA的表达。受体结合分析及IFN-θ诱导ISGs基因分析表明,IFN-θ分子能与IFNαR胞外区发生特异性结合反应,激活下游JAK/STAT信号通路,产生ISGF3聚合物并与ISRE结合,最终引起ISGs基因的上调表达。最后我们分析了IFN-θ对其他细胞因子的影响,实验结果表明IFN-θ能够使IL-6、IL-12及IFN-γ三种细胞因子的表达上调,说明IFN-θ对免疫系统存在潜在的调节作用。综上所述,IFN-θ不仅在序列上与其他I型干扰素有较高的同源性,在抗病毒、受体结合、诱导表达等多个方面符合I型干扰素的共同特征,因此我们认为IFN-θ是I型干扰素基因家族中一个新的亚型。
第三章:猪干扰素-alpha用作抗口蹄疫病毒重组多肽疫苗佐剂的研究
在本项研究中,我们将猪干扰素-alpha(PoIFN-α)制备的核酸佐剂与抗口蹄疫基因工程多肽疫苗联合免疫动物,检测猪干扰素-alpha在动物体内的佐剂效果。首先,将PoIFN-α基因克隆入pcDNA3真核表达载体中,筛选阳性克隆后大量抽提质粒,通过脱水化-再水化步骤将重组质粒包裹入阳离子脂质体内制备成核酸佐剂(IFN-adjuvant)。该佐剂与低剂量的多肽疫苗联合注射家猪。检测结果表明,佐剂与疫苗联用可以强烈地诱导动物体产生FMDV中和抗体和T细胞介导的免疫反应;然而在只注射低剂量的多肽疫苗的动物体内,我们只检测到温和的细胞免疫和体液免疫反应。作为蛋白疫苗的佐剂,PoIFN-α能够诱导炎症因子(inflammatory cytokine)在动物体内的强烈表达,这个结果表明干扰素佐剂和多肽疫苗能够使原T辅助细胞向I型辅助细胞(Th1)分化。对动物体内PoIFN-α含量测定结果表明,重组蛋白疫苗能够与干扰素佐剂协同反应产生内源性IFN-α的表达。在病毒攻击实验中,所有的对照组动物均出现口蹄疫临床症状;然而佐剂和疫苗联合注射组的动物均得到保护,没有发现病毒血症和口蹄部水疱,对该组的病毒非结构蛋白抗体检测表明,攻毒14天后没有发现病毒在动物体内复制。根据以上结果,我们认为猪干扰素-alpha是抗口蹄疫病毒多肽重组疫苗的高效佐剂,能够有效的辅助多肽疫苗提高动物体内的免疫反应并保护动物免受口蹄疫病毒的感染。
The availability of data on the pig genome sequence prompted us to characterize the porcine IFN-α(PoIFN-α) multigene family.Fourteen functional PoIFN-αgenes and two PoIFN-αpseudogenes were detected in the porcine genome. Multiple sequence alignment revealed a C-terminal deletion of eight residues in six subtypes.A phylogenetic tree of the porcine IFN-αgene family defined the evolutionary relationship of the various subtypes.In addition,analysis of the evolutionary rate and the effect of positive selection suggested that the C-terminal deletion is a strategy for preservation in the genome.Eight PoIFN-αsubtypes were isolated from the porcine liver genome and expressed in BHK-21 cells line.We detected the level of transcription by real-time quantitative RT-PCR analysis.The antiviral activities of the products were determined by WISH cells/Vesicular Stomatitis Virus(VSV) and PK 15 cells/Pseudorabies Virus(PRV) respectively.We found the antiviral activities of intact PoIFN-αgenes are approximate 2-50 times higher than those of the subtypes with C-terminal deletions in WISH cells and 15-55 times higher in PK 15 cells.There was no obvious difference between the subtypes with and without C-terminal deletion on acid susceptibility.For investigating the virus-inducing expression profile of PoIFN-αsubtypes,the expression of PoIFN-αwas detected using the two PCR strategies in three systems,namely,the Poly(I). Poly(C)-DEAE-dextran-induced PK 15 cells,the Pseudorabies Virus-infected PK 15 cells and the infected PK 15 cells with attenuated strain of Swine Fever Virus respectively.In Poly(I).Poly(C)-DEAE-dextran induced PK 15 cells,the expression of IFN-α2,-α3,-α4,-α8,-α9 after 6h/24h inducement in PK 15 cells were observed. In Pseudorabies Virus-infected PK 15 cells,the expression of PoIFN-α2,-α3,-α8,-α9, -α10,and -α13 was observed after 6h/24h infection and in attenuated strain of Swine Fever Virus-infected PK 15 cells,the upregulation of PoIFN-α2,-α3,-α4,-α8,-α9, and -α10 was detected.The results of Real-time quantitative PCR analysis suggested that the expression was time-dependent in Pseudorabies Virus/Poly(I). Poly(C)-DEAE-dextran induced PK 15 cells.But in attenuated strain of Swine Fever Virus-infected PK 15 system,the expression level of IFN-αsubtypes was not obviously time dependent.
From the data of the pig genome sequence,we obtained a group of new interferon-like sequences,which have intact ORF to code 167AA-184AA peptides. The peptides have 23%-59%amino acid identities to the typeⅠinterferon as known. The prediction of conserved domain suggested those interferon-like peptides possess the typeⅠinterferon conserved domain,and then the phylogenetic analysis showed that those sequences have close relationship with mouse IFN-ζand porcine IFN-δ. Therefore,we classified those peptides to typeⅠinterferon family and nominated them as interferon-θ.IFN-θmultigene family consists of eight subtypes,including five functional subtypes and three pseudogenes.In functional genes,IFN-θ2/-θ3 and IFN-θ4/-θ5 have high sequence homology respectively.However,IFN-θ1 has about 80%sequence similarity to the other four subtypes.In this work,we designed the PCR primers and obtained the five IFN-θfunctional genes from porcine liver genomic DNA.Three subtypes(IFN-θ1、IFN-θ2、IFN-θ5) were chosen to be inserted into the pcDNA4 vactor,and then the reconstructed plasmids were used to transfect BHK-21 cell lines.After 48hr inoculation,we collected the supernatants to determine the antiviral activity of IFN-θ.The results showed that all IFN-θs possess antiviral activities in PK-15 and IBRS-2 porcine kidney cell lines,but the three IFN-θsubtypes had obvious difference in antiviral activity.For investigating the virus-inducing expression profile of IFN-θsubtypes,we induced IBRS-2 cell using PRV,attenuated strain of SFV and Poly IC.After 6hr and 18hr inducing,we detected the up-regulation of all IFN-θmRNA using quantitative RT-PCR analysis.The receptor analysis and ISGs gene inducing analysis suggested that IFN-θs especially bind to extra-cellular domain of IFNαR and activate the JAK/STAT signaling pathway to up-regulate ISGs expression.At last,we analyzed the cytokines expression after IFN-θinducement.The results showed that IFN-θstimulate the expression of IL-6、IL-12 and IFN-γ,which suggested that IFN-θcould have the regulative function to immune system.On the basis of our results,IFN-θnot only has the sequence homology to other typeⅠinterferons,but also matches the primary properties of typeⅠinterferons in antiviral, IFNαR receptor binding and virus inducing,etc.So we figured that IFN-θis a new subtype of typeⅠinterferon family.
The adjuvant effect of porcine interferon alpha(PoIFN-α) was examined in swine vaccinated with a recombinant FMD protein vaccine named IgG-FMDV, which contains the swine IgG single heavy chain constant region and an immunogenic peptide of serotype O FMDV.The PoIFN-αgene was cloned into pcDNA3 vector and the recombinant plasmid was incorporated into cationic liposomes by a dehydration and rehydration procedure to use as an adjuvant,injected together with low-dose IgG-FMDV.This procedure resulted in strong induction of FMDV-specific neutralizing antibody and significant T cell-mediated immune responses,whereas only a modest humoral and cellular response was observed with low dose vaccine alone.As an adjuvant for the protein vaccine,PoIFN-αinduced strong inflammatory cytokine production in vivo and the results denoted that IFN-adjuvant and our vaccines could drive the immune response toward Th1 type responses.The data of ELISA suggests that the recombinant protein vaccine synergizes with the IFN-adjuvant to produce endogenous IFN in vivo.In response to viral challenge,all control animals developed viremia and lesions,whereas all animals received IFN-adjuvant+IgG-FMDV were protected and nonstructural protein antibody in this group could not be detected by 14 days post-challenge(dpc).Our studies indicate that porcine IFN-αis a powerful adjuvant for recombinant FMD protein vaccine and could aid in vaccination against FMDV in swine.
家猪基因组测序计划(Swine Genome Sequencing Project)提供的序列数据使得我们能够对猪IFN-α多基因家族的性质进行系统的分析。通过BLAST的方法,我们从已提交的序列工作草图中获得了16条IFN-α亚型的基因序列(Porcine interferon-α,PoIFN-α),其中包括14条功能基因和2条假基因。多序列比对发现,有6条功能基因编码的蛋白在C端出现了8个氨基酸的缺失。构建的PoIFN-α多基因家族系统发生树揭示各亚型之间的进化关系。除此以外,对PoIFN-α蛋白分子C端的进化速率分析和阳性选择分析说明C末端的缺失不是某些亚型向假基因进化的标志,而是在基因组中保持进化优势的一种策略。为了进一步分析PoIFN-α家族的性质,从猪的肝脏基因组中分离出了8种不同的PoIFN-α亚型基因,然后将这些基因克隆入真核表达载体中,筛选阳性克隆后重组质粒转染BHK-21细胞并表达48小时收集上清液。转染效率通过荧光定量RT-PCR标定,使其保持一致。分别利用WISH细胞/VSV病毒和PK-15细胞/PRV病毒两种干扰素检测系统测定细胞转染上清液中的抗病毒活性。实验结果表明完整的PoIFN-α亚型的抗病毒活性在WISH细胞中比C端缺失的亚型高2-50倍,在PK-15细胞中比C端缺失的亚型高15-55倍。但是没有发现尾部的缺失对PoIFN-α的酸稳定性产生影响。为了进一步分析PoIFN-α各亚型在不同病毒诱导条件下的表达情况,我们采用了两种PCR检测策略:对每种亚型设计特异性引物检测和设计PoIFN-α通用引物检测。实验结果表明,在Poly IC-DEAE-dextran诱导的PK15细胞中,PoIFN-α2、-α3、-α4、-α8、-α9五种亚型在诱导6hr/24hr后得到了表达;在PRV感染的PK15细胞中,PoIFN-α2、-α3、-α8、-α9、-α10、-α13六种亚型的表达出现上调;在SFV弱毒株感染的PK15细胞中PoIFN-α2、-α3、-α4、-α8、-α9、-α10六种亚型在诱导后得到表达。荧光定量PCR分析的结果表明,Poly IC-DEAE-dextran和PRV诱导的PK15细胞中PoIFN-α的表达上调存在时间依赖性,而SFV弱毒株感染的PK15细胞中PoIFN-α的表达在6hr和24hr没有明显的不同。
第二章:干扰素-θ,一种哺乳动物新型干扰素基因家族性质的研究
通过对家猪基因组测序计划提交的工作草图序列进行生物信息学分析,我们发现了一组干扰素基因近似序列。该组基因编码的蛋白质与其他I型干扰素存在23%-59%的氨基酸序列同源性,SMART软件预测发现其具有I型干扰素的保守结构域,同时进化分析表明该基因家族与小鼠的IFN-ζ基因及家猪的IFN-δ具有较近的系统发生关系,综合以上几点我们认为该组基因是一个新型的I型干扰素基因家族,命名为IFN-θ。IFN-θ基因家族由8个亚型组成,其中有5个亚型编码具有生物功能的蛋白质,而其他3个亚型为假基因。在5个功能亚型中,IFN-θ2与IFN-θ3、IFN-θ4与IFN-θ5分别具有很高的序列同源性,而IFN-θ1与其他4个亚型均有80%左右同源性。我们根据基因组分析得到的序列设计引物并以家猪肝脏基因组DNA为模板,利用PCR的方法分离到了5条IFN-θ功能基因。将IFN-θ的三种亚型(IFN-θ1、IFN-θ2、IFN-θ5)克隆入真核表达载体并转染细胞,经过48小时表达后收集上清液,生物活性分析表明IFN-θ的三种亚型在PK-15细胞和IBRS-2细胞中均有抗病毒功能,但是三个亚型的抗病毒活性明显不同。在病毒诱导表达谱分析中,PRV、SFV减毒株及Poly IC均能够在不同时间点在IBRS-2细胞中诱导IFN-θmRNA的表达。受体结合分析及IFN-θ诱导ISGs基因分析表明,IFN-θ分子能与IFNαR胞外区发生特异性结合反应,激活下游JAK/STAT信号通路,产生ISGF3聚合物并与ISRE结合,最终引起ISGs基因的上调表达。最后我们分析了IFN-θ对其他细胞因子的影响,实验结果表明IFN-θ能够使IL-6、IL-12及IFN-γ三种细胞因子的表达上调,说明IFN-θ对免疫系统存在潜在的调节作用。综上所述,IFN-θ不仅在序列上与其他I型干扰素有较高的同源性,在抗病毒、受体结合、诱导表达等多个方面符合I型干扰素的共同特征,因此我们认为IFN-θ是I型干扰素基因家族中一个新的亚型。
第三章:猪干扰素-alpha用作抗口蹄疫病毒重组多肽疫苗佐剂的研究
在本项研究中,我们将猪干扰素-alpha(PoIFN-α)制备的核酸佐剂与抗口蹄疫基因工程多肽疫苗联合免疫动物,检测猪干扰素-alpha在动物体内的佐剂效果。首先,将PoIFN-α基因克隆入pcDNA3真核表达载体中,筛选阳性克隆后大量抽提质粒,通过脱水化-再水化步骤将重组质粒包裹入阳离子脂质体内制备成核酸佐剂(IFN-adjuvant)。该佐剂与低剂量的多肽疫苗联合注射家猪。检测结果表明,佐剂与疫苗联用可以强烈地诱导动物体产生FMDV中和抗体和T细胞介导的免疫反应;然而在只注射低剂量的多肽疫苗的动物体内,我们只检测到温和的细胞免疫和体液免疫反应。作为蛋白疫苗的佐剂,PoIFN-α能够诱导炎症因子(inflammatory cytokine)在动物体内的强烈表达,这个结果表明干扰素佐剂和多肽疫苗能够使原T辅助细胞向I型辅助细胞(Th1)分化。对动物体内PoIFN-α含量测定结果表明,重组蛋白疫苗能够与干扰素佐剂协同反应产生内源性IFN-α的表达。在病毒攻击实验中,所有的对照组动物均出现口蹄疫临床症状;然而佐剂和疫苗联合注射组的动物均得到保护,没有发现病毒血症和口蹄部水疱,对该组的病毒非结构蛋白抗体检测表明,攻毒14天后没有发现病毒在动物体内复制。根据以上结果,我们认为猪干扰素-alpha是抗口蹄疫病毒多肽重组疫苗的高效佐剂,能够有效的辅助多肽疫苗提高动物体内的免疫反应并保护动物免受口蹄疫病毒的感染。
The availability of data on the pig genome sequence prompted us to characterize the porcine IFN-α(PoIFN-α) multigene family.Fourteen functional PoIFN-αgenes and two PoIFN-αpseudogenes were detected in the porcine genome. Multiple sequence alignment revealed a C-terminal deletion of eight residues in six subtypes.A phylogenetic tree of the porcine IFN-αgene family defined the evolutionary relationship of the various subtypes.In addition,analysis of the evolutionary rate and the effect of positive selection suggested that the C-terminal deletion is a strategy for preservation in the genome.Eight PoIFN-αsubtypes were isolated from the porcine liver genome and expressed in BHK-21 cells line.We detected the level of transcription by real-time quantitative RT-PCR analysis.The antiviral activities of the products were determined by WISH cells/Vesicular Stomatitis Virus(VSV) and PK 15 cells/Pseudorabies Virus(PRV) respectively.We found the antiviral activities of intact PoIFN-αgenes are approximate 2-50 times higher than those of the subtypes with C-terminal deletions in WISH cells and 15-55 times higher in PK 15 cells.There was no obvious difference between the subtypes with and without C-terminal deletion on acid susceptibility.For investigating the virus-inducing expression profile of PoIFN-αsubtypes,the expression of PoIFN-αwas detected using the two PCR strategies in three systems,namely,the Poly(I). Poly(C)-DEAE-dextran-induced PK 15 cells,the Pseudorabies Virus-infected PK 15 cells and the infected PK 15 cells with attenuated strain of Swine Fever Virus respectively.In Poly(I).Poly(C)-DEAE-dextran induced PK 15 cells,the expression of IFN-α2,-α3,-α4,-α8,-α9 after 6h/24h inducement in PK 15 cells were observed. In Pseudorabies Virus-infected PK 15 cells,the expression of PoIFN-α2,-α3,-α8,-α9, -α10,and -α13 was observed after 6h/24h infection and in attenuated strain of Swine Fever Virus-infected PK 15 cells,the upregulation of PoIFN-α2,-α3,-α4,-α8,-α9, and -α10 was detected.The results of Real-time quantitative PCR analysis suggested that the expression was time-dependent in Pseudorabies Virus/Poly(I). Poly(C)-DEAE-dextran induced PK 15 cells.But in attenuated strain of Swine Fever Virus-infected PK 15 system,the expression level of IFN-αsubtypes was not obviously time dependent.
From the data of the pig genome sequence,we obtained a group of new interferon-like sequences,which have intact ORF to code 167AA-184AA peptides. The peptides have 23%-59%amino acid identities to the typeⅠinterferon as known. The prediction of conserved domain suggested those interferon-like peptides possess the typeⅠinterferon conserved domain,and then the phylogenetic analysis showed that those sequences have close relationship with mouse IFN-ζand porcine IFN-δ. Therefore,we classified those peptides to typeⅠinterferon family and nominated them as interferon-θ.IFN-θmultigene family consists of eight subtypes,including five functional subtypes and three pseudogenes.In functional genes,IFN-θ2/-θ3 and IFN-θ4/-θ5 have high sequence homology respectively.However,IFN-θ1 has about 80%sequence similarity to the other four subtypes.In this work,we designed the PCR primers and obtained the five IFN-θfunctional genes from porcine liver genomic DNA.Three subtypes(IFN-θ1、IFN-θ2、IFN-θ5) were chosen to be inserted into the pcDNA4 vactor,and then the reconstructed plasmids were used to transfect BHK-21 cell lines.After 48hr inoculation,we collected the supernatants to determine the antiviral activity of IFN-θ.The results showed that all IFN-θs possess antiviral activities in PK-15 and IBRS-2 porcine kidney cell lines,but the three IFN-θsubtypes had obvious difference in antiviral activity.For investigating the virus-inducing expression profile of IFN-θsubtypes,we induced IBRS-2 cell using PRV,attenuated strain of SFV and Poly IC.After 6hr and 18hr inducing,we detected the up-regulation of all IFN-θmRNA using quantitative RT-PCR analysis.The receptor analysis and ISGs gene inducing analysis suggested that IFN-θs especially bind to extra-cellular domain of IFNαR and activate the JAK/STAT signaling pathway to up-regulate ISGs expression.At last,we analyzed the cytokines expression after IFN-θinducement.The results showed that IFN-θstimulate the expression of IL-6、IL-12 and IFN-γ,which suggested that IFN-θcould have the regulative function to immune system.On the basis of our results,IFN-θnot only has the sequence homology to other typeⅠinterferons,but also matches the primary properties of typeⅠinterferons in antiviral, IFNαR receptor binding and virus inducing,etc.So we figured that IFN-θis a new subtype of typeⅠinterferon family.
The adjuvant effect of porcine interferon alpha(PoIFN-α) was examined in swine vaccinated with a recombinant FMD protein vaccine named IgG-FMDV, which contains the swine IgG single heavy chain constant region and an immunogenic peptide of serotype O FMDV.The PoIFN-αgene was cloned into pcDNA3 vector and the recombinant plasmid was incorporated into cationic liposomes by a dehydration and rehydration procedure to use as an adjuvant,injected together with low-dose IgG-FMDV.This procedure resulted in strong induction of FMDV-specific neutralizing antibody and significant T cell-mediated immune responses,whereas only a modest humoral and cellular response was observed with low dose vaccine alone.As an adjuvant for the protein vaccine,PoIFN-αinduced strong inflammatory cytokine production in vivo and the results denoted that IFN-adjuvant and our vaccines could drive the immune response toward Th1 type responses.The data of ELISA suggests that the recombinant protein vaccine synergizes with the IFN-adjuvant to produce endogenous IFN in vivo.In response to viral challenge,all control animals developed viremia and lesions,whereas all animals received IFN-adjuvant+IgG-FMDV were protected and nonstructural protein antibody in this group could not be detected by 14 days post-challenge(dpc).Our studies indicate that porcine IFN-αis a powerful adjuvant for recombinant FMD protein vaccine and could aid in vaccination against FMDV in swine.
引文
[1]Isaacs,A.and Lindenmann,J.1957.Virus interference.Ⅰ.The interferon.Proc.R.Soc.Lond.Ser.B Biol.Sci.147,258-267.
[2]Pestka,S.,Krause,C.D.,Walter,M.R.2004.Interferon,interferon-like cytokines,and their receptors.Immunological Reviews 202,8-32.
[3]Sen,G.C.and Lengyel,P.1992.The interferon system.A bird's eye view of its biochemistry.J.Biol.Chem.267,5017-5020.
[4]Jin,B.Q.2001.Cellular and molecular immunology[M].pp.131-239,Beijing:Science Press.(In Chinese)
[5]Huising,M.O.,Kruiswijk,C.P.,Flik,G.2006.Phylogeny and evolution of class-Ⅰ helical cytokines.Journal of Endocrinology 189,1-25.
[6]Pestka,S.,Krause,C.D.,Sarkar,D.,Walter,M.R.,Shi,Y.F.,Fisher,P.B.2004.Interleukin-10 and related cytokines and receptors.Annu.Rev.Immunol.22,929-979.
[7]Krausea,C.D.and Pestka,S.2005.Evolution of the Class 2 cytokines and receptors,and discovery of new friends and relatives.Pharmacology &Therapeutics 106,299-346.
[8]Bazan,J.F.1990.Structural design and molecular evolution of a cytokine receptor superfamily.Proc.Natl.Acad.Sci.U.S.A.87,6934-6938.
[9]Thoreau,E.,Petridou,B.,Kelly,P.A.,Djiane,J.,Mornon,J.P.1991.Structural symmetry of the extracellular domain of the cytokine/growth hormone/prolactin receptor family and interferon receptors revealed by hydrophobic cluster analysis.FEBS Letters 282,26-31.
[10]Langer,J.A.,Cutrone,E.C.,Kotenko,S.2004.The class Ⅱ cytokine receptor (CRF2) family:overview and patterns of receptor-ligand interactions.Cytokine Growth Factor Rev.15,33-48.
[11]Sidney,P.,et al.1981.Defination and classification of the interferon.In: Methodsin Enzymology, Vol. 78, pp. 3-28, New York: Academic Press.
[12] Pestka, S., Langer, J.A., Zoon, K.C., Samuel, C.E. 1987. Interferons and their actions. Ann. Rev. Biochem. 56,727-777.
[13] Goeddel, D.V., Leung, D.W., Dull, T.J., Gross, M., Lawn, R.M., Mccandliss, R., Seeburg, P.H., Ullrich, A., Yelverton, E., Gray, P.W. 1981. The structure of eight distinct cloned human leukocyte interferon cDNA. Nature 290,20-26.
[14] Lengyel, P. 1982. Biochemistry of interferon and their actions. Ann. Rev. Biochem. 51,251-282.
[15] Ealick, S.E., Cook, W.J., Vijaykumar, S., Carson, M., Nagabhushan, T.L., Trotta, P.P., Bugg, C.E. 1991. Three-dimensional structure of recombinant human interferon-γ. Science 252, 698-702.
[16] Fish, E.N., Banerjee, K., Stebbing, N., 1989. The role of 3 domains in the biological-activity of human interferon-alpha. J Interferon Res. 9,97-114.
[17] Seto, M.H., Harkins, R.N., Adler, M., Whitlow, M, Church, W.B., Croze, E. 1995. Homology model of human interferon-a8 and its receptor complex. Protein Sci. 4,655-670.
[18] Yip,Y.K., Barrowclough, B.S., Urban, C, Vilcek, J. 1982. Molecular weight of human gamma interferon is similar to that of other human interferons. Science 215,411-413.
[19] Sareneva, T., Mortz, E., Tolo, H., Roepstorff, P., Julkunen, T. 1996 Biosynthesis and N-glycosylation of human interferon-gamma-Asn25 and Asn97 differ markedly in how efficiently they are glycosylated and in their oligosaccharide composition. Eur. J. Biochem. 242,191-200.
[20] Lefevre, F., Guillomot, M., D'Andrea, S., Battegay, S., La Bonnardiere, C. 1998. Interferon-detla: the first member of a novel type I interferon family. Biochimie 80,779-788.
[21] Roberts, R.M., Cross, J.C., Leaman, D.W. 1991. Unique features of the trophoblast interferons. Pharmacol. Ther. 51, 329-345.
[22] Oritani, K., Medina, K.L., Tomiyama, Y, Ishikawa, J., Okajima, Y, Ogawa, M., Yokota, T., Aoyama, K., Takahashi, I., Kincade, P.W., Matsuzawa, Y 2000. Limitin: an interferon-like cytokine that preferentially influences B lymphocyte precursors. Nat. Med. 6,659-666.
[23] van Pesch, V., Lanaya, H., Renauld, J.C., Michiels, T. 2004. Characterization of the murine alpha interferon gene family. Journal of virology 78, 8219-8228.
[24] Cheng, G., Chen, W.Z., Li, Z.F., Yan, W.Y., Zhao, X., Xie, J., Liu, M.Q., Zhang, H., Zhong, Y., Zheng, Z.X. 2006. Characterization of the porcine alpha interferon multigene family. Gene 382,28-38.
[25] Hardy, M.P., Owczarek, C.M., Jermiin, L.S., Ejdeback, M., Hertzog, P.J. 2004. Characterization of the type I interferon locus and identification of novel genes. Genomics 84,331-345.
[26] Adolf, G.R., Fruhbeis, B., Hauptmann, R., Kalsner, I., Maurerfogy, I., Ostermann, E., Patzelt, E., Schwendenwein, R., Sommergruber, W., Zophel, A. 1991. Human interferon omega 1: isolation of the gene, expression in Chinese hamster ovary cells and characterization of the recombinant protein. Biochim. et. Biophys. Acta 1089,167-174.
[27] Chen, J, Wood, W.I. 2003. Interferon PRO655. pp. 1-37, Genentech. [US 6,300,475] [Patent].
[28] Oritani, K., Kincade, P.W., Zhang, C., Tomiyama, Y., Matsuzawa, Y. 2001. Type I interferons and limitin: a comparison of structures, receptors, and functions. Cytokine & Growth Factor Rev. 12, 337-348.
[29] LaFleur, D.W., Nardelli, B., Tsareva, T., et al. 2001. IFN-κ, a novel type I interferon expressed in human keratinocytes. J. Biol. Chem. 276, 39765-39771.
[30] Nardelli, B., Zaritskaya, L., Semenuk, M., Cho, Y.H., La Fleur, D.W., Shah, D., Ullrich, S., Girolomoni, G., Albanesi, C., Moore, P.A. 2002. Regulatory effect of IFN-κ, A novel type I IFN, on cytokine production by cell of the innate immune system. J. Immunol. 169,4822-4830.
[31] Demmers, K.J., Derecka, K., Flint, A. 2001. Trophoblast interferon and pregnancy. Reproduction 121,41-49.
[32] Roberts, R.M., Ealy, A.D., Alexenko, A.P., Han, C.S., Ezashi, T. 1999. Trophoblast interferons. Placenta 20,259-264.
[33] Kotenko, S.V., Gallagher, G., Baurin, V.V., Lewis-Antes, A., Shen, M., Shah, N.K., Langer, J.A., Sheikh, F., Dickensheets, H., Donnelly, R.P. 2003. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat. Immunol. 4, 69-77.
[34] Sheppard, P, Kindsvogel, W., Xu, W.F., et al. 2003. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat. Immunol. 4, 63-68.
[35] Stark, G.R., Kerr, I.M., Williams, B.R., Silverman, R.H., Schreiber, R.D. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67,227-264.
[36] Pestka, S., Kotenko, S.V., Muthukumaran, G., Izotova, L., Cook, J.R., Garotta, G. 1997. The interferon γ(IFN-γ) receptor: a paradigm for the multichain cytokine receptor. Cytokine Growth Factor Rev. 8,189-206.
[37] Pestka, S. 1997. The interferon receptors. Semin. Oncol. 24, S9.
[38] Uze, G., Lutfalla, G., Gresser, I. 1990. Genetic transfer of a functional human interferon a receptor into mouse cells: cloning and expression of its cDNA. Cell 60,225-234.
[39] Darnell, J.E. Jr. 1997. STATs and gene regulation. Science 277,1630-1635.
[40] Schindler, C., Fu, X.Y., Improta, T., Aebersold, R., Darnell, J.E. Jr. 1992. Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc. Natl. Acad. Sci. U. S. A. 89,7836-7839.
[41] Fu, X.Y., Schindler, C., Improta, T, Aebersold, R., Darnell, J.E. Jr. 1992. The roteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc. Natl. Acad. Sci. U. S. A. 89, 7840-7843.
[42] Nguyen, K.B., Watford, W.T., Salomon, R., Hofmann, S.R., Pien, G.C., Morinobu, A., Gadina, M., O'Shea, J.J., Biron, C.A. 2002. Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection. Science 297,2063-2066.
[43] Su, L. and David, M. 2000. Distinct mechanisms of STAT phosphorylation via the interferon-alpha/ beta receptor. Selective inhibition of STAT3 and STAT5 by piceatannol. J Biol. Chem. 275,12661-12666.
[44] Soh, J., Donnelly, R.J., Kotenko, S., Mariano, T.M., Cook, J.R., Wang, N., Emanuel, S., Schwartz, B., Miki, T., Pestka, S. 1994. Identification and sequence of an accessory factor required for activation of the human interferon-gamma receptor. Cell 76, 793-802.
[45] Hemmi, S., Bohni, R., Stark, G., Di Marco, F., Aguet, M. 1994. A novel member of the interferon receptor family complements functionality of the murine interferon gamma receptor in human cells. Cell 76, 803-810.
[46] Shuai, K., Schindler, C., Prezioso, V.R., Darnell, J.E. Jr. 1992. Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science 258,1808-1812.
[47] Shuai, K., Stark, G.R., Kerr, I.M., Darnell, J.E. Jr. 1993. A single phosphotyrosine residue of STAT91 required for gene activation by interferon-gamma. Science 261, 1744-1746.
[48] Durbin, J.E., Hackenmiller, R., Simon, M.C., Levy, D.E. 1996. Targeted disruption of the mouse STAT1 gene results in compromised innate immunity to viral disease. Cell 84,443-450.
[49] Eilers, A. and Decker, T. 1995. Activity of STAT family transcription factors is developmentally controlled in cells of the macrophage lineage. Immunobiology 193, 328-333.
[50] Krause, C.D., Mei, E.W, Xie, J.X., Jia, Y.W, Bopp, M.A., Hochstrasser, R.M., Pestka, S. 2002. Seeing the light: preassembly and ligand-induced changes of the interferon gamma receptor complex in cells. Mol. Cell. Proteomics 1, 805-815.
[51] David, M. 2002. Signal transduction by type I interferons. Biotechniques Suppl. 58-65.
[52] Takaoka, A., Hayakawa, S., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., Sasaki, S., Imai, K., Shibue, T., Honda, K., Taniguchi, T. 2003. Integration of interferonalpha/ beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 424, 516-523.
[53] Abramovich, C., Yakobson, B., Chebath, J., Revel, M. 1997. A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor. EMBO J 16, 260-266.
[54] Chung, C.D., Liao, J.Y., Liu, B., Rao, X.P., Jay, P., Berta, P., Shuai, K. 1997. Specific inhibition of STAT3 signal transduction by PIAS3. Science 278, 1803-1805.
[55] Kile, B.T., Schulman, B.A., Alexander, W.S., Nicola, N.A., Martin, H.M., Hilton, D.J. 2002. The SOCS box: a tale of destruction and degradation. Trends Biochem. Sci. 27,235-241.
[56] Kim, T.K. and Maniatis, T. 1996. Regulation of interferon-gamma-activated STATl by the ubiquitin-proteasome pathway. Science 273,1717-1719.
[57] Radhakrishnan, R., Walter, L.J., Hruza, A., Reichert, P., Trotta, P.P., Nagabhushan, T.L., Walter, M.R. 1996. Zinc mediated dimer of human interferon-alpha2b revealed by X-ray crystallography. Structure 4,1453-1463.
[58] Klaus, W., Gsell, B., Labhardt, A.M., Wipf, B., Senn, H. 1997. The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution. J Mol. Biol. 274, 661-675.
[59] Karpusas, M., Nolte, M., Benton, C.B., Meier, W., Lipscomb, W.N., Goelz, S. 1997. The crystal structure of human interferon beta at 2.2-A° resolution. Proc. Natl.Acad. Sci. U. S.A. 94,11813-11818.
[60] Radhakrishnan, R., Walter, L.J., Subramaniam, P.S., Johnson, H.M., Walter, M.R. 1999. Crystal structure of ovine interferon-tau at 2.1 A° resolution. J Mol. Biol. 286, 151-162.
[61] Walter, M.R, Windsor, W, Nagabhushan, T.L, Lundell, D.J, Lunn, C.A., Zauodny, P.J., Narula, S.K. 1995. Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor. Nature 376,230-235.
[62] Thiel, D.J, le Du, M.H, Walter, R.L, D'Arcy, A, Chene, C, Fountoulakis, M, Garotta, G, Winkler, F.K, Ealick, S.E. 2000. Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex. Structure Fold Des. 8,927-936.
[63] Randal, M. and Kossiakoff, A.A. 2001. The structure and activity of a monomeric interferon-gamma: alpha-chain receptor signaling complex. Structure (Camb) 9,155-163.
[64] Rubinstein, M, Rubinstein, S, Familletti, P.C., Miller, R.S, Waldman, A.A. 1978. Human leukocyte interferon purified to homogeneity. Science 202, 1289-1290.
[65] Pestka, S. 1983. The human interferons-from protein purification and sequence to cloning and expression in bacteria: before, between, beyond. Arch. Biochem. Biophys. 221, 1-37.
[66] Pestka, S. 2000. The human interferon alpha species and receptors. Biopolymers 55,254-287.
[67] Evinger, M., Rubinstein, M., Pestka, S. 1981. Antiproliferative and antiviral activities of human leukocyte interferons. Arch. Biochem. Biophys. 210, 319-329.
[68] Pestka, S. 1997. The human interferon-alpha species and hybrid proteins. Semin. Oncol. 24, S9.
[69] Ortaldo, J.R. Herberman, R.B, Harvey, C., Osheroff, P, Pan, Y.C.E., Kelder, B, Pestka, S. 1984. A species of human alpha interferon that lacks the ability to boost human natural killer activity. Proc. Natl. Acad. Sci. U. S. A. 81, 4926-4929.
[70] Ortaldo, J.R., et al. 1983. Augmentation of NK activity with recombinant and hybrid recombinant human leukocyte interferons. In: De Maeyer E, Schellekens H, eds. The Biology of the Interferon System. pp. 353-358, Amsterdam: Elsevier Science Publishers.
[71] van Pesch, V. and Michiels, T. 2003. Characterization of interferon-alpha 13, a novel constitutive murine interferon-alpha subtype. J. Biol. Chem. 278, 46321-46328.
[72] Nguyen, H., Hiscott, J., Pitha, P. M. 1997. The growing family of interferon regulatory factors. Cytokine Growth Factor Rev. 8,293-312.
[73] Mamane, Y., Heylbroeck, C., Genin, P., Algarte, M., Servant, M.J., LePage, C., De Luca, C., Kwon, H., Lin, R.T., Hiscott, J. 1999. Interferon regulatory factors: the next generation. Gene 237,1-14.
[74] Taniguchi, T., Tanaka, N., Ogasawara, K., Taki, S., Sato, M., Takaoka, A. 2000. The transcription factor IRF-1 and its family members in the regulation of host defense. Cold Spring Harb. Symp. Quant. Biol. 64,465-472.
[75] Taniguchi, T., Ogasawara, K., Takaoka, A. Tanaka, N. 2001. IRF family of transcription factors as the regulators of host defense. Annu. Rev. Immunol. 19, 623-655.
[76] Lin, R., Mamane, Y. Hiscott, J. 2000. Multiple regulatory domains control IRF-7 activity in response to virus infection. J. Biol. Chem. 275, 34320-34327.
[77] Yeow, W. S., Au, W.C., Juang, Y.T, Fields, C.D., Dent, C.L., Gewert, D.R., Pitha, P.M. 2000. Reconstitution of virus-mediated expression of interferon alpha genes in human fibroblast cells by ectopic interferon regulatory factor-7. J. Biol. Chem. 275,6313-6320.
[78] Sato, M., Suemori, H., Hata, N., Asagiri, M., Ogasawara, K., Nakao, K., Nakaya, T., Katsuki, M., Noguchi, S., Tanaka, N., Taniguchi, T. 2000. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-α/β gene induction. Immunity 13, 539-548.
[79] Braganca, J., Genin, P., Bandu, M.T., Darracq, N., Vignal, R., Casse, C., Doly, J., Civas, A. 1997. Synergism between multiple virus-induced factor binding elements involved in the differential expression of interferon alpha genes. J. Biol. Chem. 272,22154-22162.
[80] Lin, R.T., Mamane, Y., Hiscott, J. 2000. Multiple regulatory domains control IRF-7 activity in response to virus infection. J. Biol. Chem. 275, 34320-34327.
[81] Juang, Y.T., Lowther, W., Kellum, M., Au, W.C., Lin, R., Hiscott, J., Pitha, P.M. 1998. Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc. Natl. Acad. Sci. U. S. A. 95, 9837-9842.
[82] Morin, P., Braganca, J., Bandu, M.T., Lin, R., Hiscott, J., Doly, J., Civas, A. 2002. Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription. J. Mol. Biol. 316,1009-1022.
[83] Torrence, P.F. et al. 1985. How interferon works. In Biological response modifiers. pp. 77-119, Orlando: Academic Press.
[84] Sandberg, K., Eloranta, M.L., Campbell, I.L. 1994. Expression of alpha/beta interferons and their relationship to IFN-alpha/beta-induced genes in lymphocytic choriomeningitis. J. Virol. 68,7358-7366.
[85] McDowell, M.A., Lucas, D.M., Nicolet, C.M., Paulnock, D.M. 1995. Differential utilization of IFN-responsive element in two maturationally distinct Macrophage cell lines. J. Immunol. 155,4933-4941.
[86] Muller, U., Steinhoff, U., Reis, L.F.L., Hemmi, S., Pavlovic, J., Zinkernagel, R.M., Aguet, M. 1994. Functional role of type I and type II interferons in antiviral defense. Science 264,1918-1921.
[87] Kaiser, P., Wain, H.M., Rothwell, L. 1998. Structure of the chicken interferon-g gene, and comparison to mammalian homologues. Gene 207, 25-32.
[88] Altmann, S.M., Mellon, M.T., Distel, D.L., Kim, C.H. 2003. Molecular and functional analysis of an interferon gene from the zebrafish, Danio rerio. J Virol. 77,1992-2002.
[89] Lutfalla, G., Crollius, H.R., Stange-thomann, N., Jaillon, O., Mogensen, K., Monneron, D. 2003. Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish. BMC Genomics 4, 1-15.
[90] Robertsen, B., Bergan, V, Rokenes, T., Larsen, R., Albuquerque, A. 2003. Atlantic salmon interferon genes: cloning, sequence analysis, expression, and biological activity. J Interferon Cytokine Res. 23, 601-612.
[91] Sick, C, Schultz, U., Staeheli, P. 1996. A family of genes coding for two serologically distinct chicken interferons. J. Biol. Chem. 271,7635-7639.
[92] Nanda, I., Sick, C., Munster, U., Kaspers, B., Schartl, M., Staeheli, P., Schmid, M. 1998. Sex chromosome linkage of chicken and duck type I interferon genes: further evidence of evolutionary conservation of the Z chromosome in birds. Chromosoma 107,204-210.
[93] Staeheli, P., Puehler, F., Schneider, K., Gobel, T.W., Kaspers, B. 2001. Cytokines of birds: conserved functions-a largely different look. J Interferon Cytokine Res. 21,993-1010.
[94] Harrison, G.A., Young, L.J., Watson, C.M., Miska, K.B., Miller, R.D., Deane, E.M. 2003. A survey of type I interferons from a marsupial and monotreme: implications for the evolution of the type I interferon gene family in mammals. Cytokine 21,105-119.
[95] Park, C., Li, S., Cha, E., Schindler, C. 2000. Immune response in STAT2 knockout mice. Immunity 13, 795-804.
[96] Roberts, R.M., Ezashi, T., Rosenfeld, C.S., Ealy, A.D., Kubisch, H.M. 2003. Evolution of the interferon tau genes and their promoters, and maternal-trophoblast interactions in control of their expression. Reproduction Suppl. 61,239-251.
[97] Pestka, S., Kelder, B., Familletti, P.C., Moschera, J.A., Crowl, R., Kempner, E.S. 1983. Molecular weight of the functional unit of human leukocyte, fibroblast, and immune interferons. J. Biol. Chem. 258,9706-9709.
[98] Igawa, D., Sakai, M., Savan, R. 2006. An unexpected discovery of two interferon gamma-like genes along with interleukin (IL)-22 and -26 from teleost: IL-22 and -26 genes have been described for the first time outside mammals. Molecular Immunology 43, 999-1000.
[99] Taya, Y., Devos, R., Tavernier, J., Cheroutre, H., Engler, G, Fiers, W. 1982. Cloning and structure of the human immune interferon-gamma chromosomal gene. EMBO J 1,953-958.
[100] Gray, P.W. and Goeddel, D.V. 1982. Structure of the human immune interferon gene. Nature 298, 859-863.
[101] Suresh, M., Karaca, K., Foster, D., Sharma, J.M. 1995. Molecular and functional characterization of turkey interferon. J. Virol. 69, 8159-8163.
[102] Schultz, U., Kock, J., Schlicht, H.J., Staeheli, P. 1995. Recombinant duck interferon: a new reagent for studying the mode of interferon action against hepatitis B virus. Virology 212,641-649.
[103] Heller, E.D., Levy, A.M., Vaiman, R., Schwartsburd, B. 1997. Chicken-embryo fibroblasts produce two types of interferon upon stimulation with Newcastle disease virus. Vet. Immunol. Immunopathol. 57, 289-303.
[104] Pene, J., Rousset, F., Briere, R, Chretien, I., Bonnefoy, J.Y., Spits, H., Yokota, T., Arai, N., Arai, K., Banchereau, J., de Vries, J. 1988. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. Proc. Natl. Acad. Sci. U. S. A. 85,6880-6684.
[105] Braun, D., Caramalho, I., Demengeot, J. 2002. IFN-alpha/beta enhances BCR-dependent B cell responses. Int. Immunol. 14,411-419.
[106] Hunter, C.A., Gabriel, K.E., Radzanowski, T., Neyer, L.E., Remington, J.S. 1997. Type I interferons enhance production of IFN-gamma by NK cells. Immunol. Lett. 59,1-5.
[107] Nistico, P., Tecce, P., Giacomini, P., Cavallari, A., Dagnano, I., Fisher, P.B., Natali, P.G 1990. Effect of recombinant human-leukocyte, fibroblast, and immune interferons on expression of class-I and class-II major histocompatibilty complex and invariant chain in early passage human-melanoma cells. Cancer Res. 50,7422-7429.
[108] Belardelli, F. 1995. Role of interferons and other cytokines in the regulation of the immune response. APMIS. 103,161-179.
[109] Montoya, M., Schiavoni, G., Mattei, F., Gresser, I., Belardelli, F., Borrow, P., Tough, D.F. 2002. Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99, 3263-3271.
[110] Santini, S.M., Lapenta, C., Logozzi, M., Parlato, S., Spada, M., Di Pucchio, T., Belardelli, F. 2000. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp. Med. 191,1777-1788.
[111] Finkelman, F.D., Svetic, A., Gresser, I., Snapper, C., Holmes, J., Trotta, P.P., Katona, I.M., Gause, W.C. 1991. Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice. J. Exp. Med. 174,1179-1188.
[112] Nakajima, H., Nakao, A., Watanabe, Y., Yoshida, S., Iwamoto, I. 1994. IFN-alpha inhibits antigen-induced eosinophil and CD4+ T cell recruitment into tissue. J. Immunol. 153,1264-1270.
[113] Taylor, J.L. and Grossberg, S.E. 1998. The effects of interferon-alpha on the production and action of other cytokines. Semin. Oncol. 25,23-29.
[114] Mitani, Y, Takaoka, A., Kim, S.H., Kato, Y, Yokachi, T., Tanaka, N., Taniguchi, T. 2001. Cross talk of the interferon-alpha/beta signaling complex with gp130 for effective interleukin-6 signaling. Genes to cells 6,631-640.
[115] Takaoka, A., Mitani, Y, Suemori, H., Sato, M., Yokochi, T., Noguchi, S., Tanaka, N., Taniguchi, T. 2000. Cross talk between interferon-gamma and -alpha/-beta signaling components in caveolar membrane domains. Science 288,2357-2360.
[116] Biron, C.A. 1998. Role of early cytokines, including alpha and beta interferons (IFN-alpha/beta), in innate and adaptive immune responses to viral infections. Seminars in immunology 10,383-390.
[117] Smith, T.J. and Wagner, R.R. 1967. Rabbit macrophage interferons. I. Conditions for biosynthesis by virus-infected and uninfected cells. J. Exp. Med. 125, 559-577.
[118] Belardelli, F., Vignaux, F., Proietti, E., Grosser, I. 1984. Injection of mice with antibody to interferon renders peritoneal macrophages permissive for vesicular stomatitis virus and encephalomyocarditis virus. Proc. Natl. Acad. Sci. U.S.A. 81,602-606.
[119] Vogel, S.N. and Fertsch, D. 1984. Endogenous interferon production by endotoxin-responsive macrophages provides an autostimulatory differentiation signal. Infect. Immun. 45,417-423.
[120] Zhang, X., Alley, E.W., Russell, S.W., Morrison, D.C. 1994. Necessity and sufficiency of beta interferon for nitric oxide production in mouse peritoneal macrophages. Infect. Immun. 62, 33-40.
[121] Gessani, S., Puddu, P., Varano, B., Borghi, P., Conti, L., Fantuzzi, L., Belardelli, F. 1994. Induction of beta interferon by human immunodeficiency virus type 1 and its gp120 protein in human monocytes-macrophages: role of beta interferon in restriction of virus replication. J. Virol. 68, 1983-1986.
[122] Meltzer, M.S., Nakamura, M., Hansen, B.D., Turpin, J.A., Kalter, D.C., Gendelman, H.E. 1990. Macrophages as susceptible targets for HIV infection, persistent viral reservoirs in tissue, and key immunoregulatory cells that control levels of virus replication and extent of disease. AIDS Res. Hum. Retroviruses. 6,967-971.
[123] Folks, T.M., Clouse, K.A., Justement, J., Rabson, A., Duh, E., Kehrl, J.H., Fauci, A.S. 1989. Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc. Natl. Acad. Sci. U. S. A. 86,2365-2368.
[124] Gendelman, H.E., Baca, L.M., Kubrak, C.A., Genis, P., Burrous, S., Friedman, R.M., Jacobs, D., Meltzer, M.S. 1992. Induction of IFN-alpha in peripheral blood mononuclear cells by HIV-infected monocytes. Restricted antiviral activity of the HIV-induced IFN. J. Immunol. 148,422-429.
[125] Cheng, G, Zhao, X., Yan W.Y., et al. 2007. Alpha interferon is a powerful adjuvant for a recombinant protein vaccine against foot-and-mouth disease virus in swine, and an effective stimulus of in vivo immune response. Vaccine 25, 5199-5208.
[126] Tough, D.F., Borrow, P., Sprent, J. 1996. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947-1950.
[127] Marrack, P., Kapoler, J., Mitchell, T. 1999. Type I interferons keep activated T cells alive. J Exp. Med. 189,521-529.
[128] Luft, T, Pang, K.C., Thomas, E., Hertzog, P., Hart, D.N.J., Trapani, J., Cebon, J. 1998. Type I IFNs enhance the terminal differentiation of dendritic cells. J. Immunol. 161,1947-1953.
[129] Paquette, R.L., Hsu, N.C., Kiertscher, S.M., Park, A.N., Tran, L., Roth, M.D., Glaspy, J.A. 1998. Interferon-alpha and granulocyte-macrophage colony stimulating factor differentiate peripheral blood monocytes into potent antigen presenting cells. J. Leukoc. Biol. 64, 358-367.
[130] Wang, J.Y., Lin, Q., Langston, H., Cooper, M.D. 1995. Resident bone marrow macrophages produce type 1 interferons that can selectively inhibit interleukin-7-driven growth of B lineage cells. Immunity 3,475-484.
[131] Su, D.M., Wang, J., Lin, Q, Cooper, M.D., Watanabe, T. 1997. Interferons α/β inhibit IL-7-induced proliferation of CD4- CD8- CD3- CD44+ CD25+ thymocytes, but do not inhibit that of CD4- CD8- CD3- CD44- CD25- thymocytes. Immunology 90,543-549.
[132] Demengeot, J., Vasconcellos, R., Modigliani, Y., Grandien, A., Coutinho, A. 1997. B lymphocyte sensitivity to IgM receptor ligation is independent of maturation stage and locally determined by macrophage-derived IFN-beta. Int. Immunol. 9,1677-1685.
[133] Vasconcellos, R., Braun, D., Coutinho, A., Demengeot, J. 1999. Type I IFN sets the stringency of B cell repertoire selection in the bone marrow. Int. Immunol. 11,279-288.
[134] Le Bon, A., Schiavoni, G, D Agostino, G, Gresser, I., Belardelli, F., Tough, D.F. 2001. Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14,461-470.
[1]Sen,G.C.and Lengyel,P.1992.The interferon system.A bird's eye view of its biochemistry.J.Biol.Chem.267,5017-5020.
[2]Flores,I.,Mariano,T.M.,Pestka,S.1991.Human interferon-co(omega) binds to the alpha/beta receptor.J.Biol.Chem.266,19875-19877.
[3]Pestka,S.,Langer,J.A.,Zoon,K.C.,Samuel,C.E.1987.Interferons and theirs actions.Annu.Rev.Biochem.56,727-777.
[4]Hardy,M.P.,Owczarek,C.M.,Jermiin,L.S.,Ejdeback,M.,Hertzog,P.J.2004.Characterization of the type Ⅰ interferon locus and identification of novel genes.Genomics 84,331-345.
[5]LaFleur,D.W.,Nardelli,B.,Tsareva,T.,Mather,D.,Feng,P.,Semenuk,M.,Taylor,K.,Buergin,M.,Chinchilla,D.,Roshke,V.,Chen,G.,Ruben,S.M.,Pitha,P.M.,Coleman,T.A.,Moore,P.A.2001.Interferon-kappa,a novel type Ⅰinterferon expressed in human keratinocytes.J.Biol.Chem.276,39765-39771.
[6]Oritani,K.,Medina,K.L.,Tomiyama,Y.,Ishikawa,J.,Okajima,Y.,Ogawa, M., Yokota, T., Aoyama, K., Takahashi, I., Kincade, P.W., Matsuzawa, Y. 2000. Limitin: an interferon-like cytokine that preferentially influences B lymphocyte precursors. Nat. Med. 6,659-666.
[7] Oritani, K., Kincade, P.W., Zhang, C., Tomiyama, Y., Matsuzawa, Y. 2001. Type I interferons and limitin: a comparison of structures, receptors, and functions. Cytokine & Growth Factor Rev. 12,337-348.
[8] Sheppard, P., Kindsvogel, W., Xu, W.F., et al. 2003. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nature Immunol. 4,63-68.
[9] Kotenko, S.V., Galagher, G., Baurin, V.V., Lewis-Antes, A., Shen, M., Shah, N.K., Langer, J.A., Sheikh, F., Dickensheets, H., Donnelly, R.P. 2003. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 4,69-77
[10] Demmers, K.J., Derecka, K., Flint, A., 2001. Trophoblast interferon and pregnancy. Reproduction 121,41-49.
[11] Lefevre, F., Guillomot, M., D'Andrea, S., Battegay, S., La Bonnardiere, C. 1998. Interferon-delta: the first member of a novel type I interferon family. Biochimie 80, 779- 788.
[12] Roberts, R.M., Ealy, A.D, Alexenko, A.P., Han, C.S., Ezashi, T. 1999. Trophoblast interferons. Placenta 20,259-264.
[13] Weissmann, C. and Weker, H. 1986. The interferon genes. Prog. Nucleic. Acid Res. Mol. Biol. 33,251-300.
[14] Diaz, M.O., Pomykala, H.M., Bohlander, S.K., Maltepe, E., Malik, K., Brownstein, B., Olopade, O.I. 1994. Structure of the human type-I interferon gene cluster determined from a YAC clone contig. Genomics 22,540-552.
[15] Kelley, K. A., Kozak, C. A., Dandoy, F., Sor, F., Skup, D., Windass, J.D., DeMaeyer-Guignard, J., Pitha, P.M., DeMaeyer, E. 1983. Mapping of murine inferferon-a genes to chromosome 4. Gene 26,181-188.
[16] Kelley, K. A. and Pitha, P. M., 1985. Characterization of a mouse interferon gene locus I. Isolation of a cluster of four a-interferon genes. Nucleic Acids Res. 13, 805-823.
[17] van Pesch, V. and Michiels, T. 2003. Characterization of interferon-alpha 13, a novel constitutive murine interferon-alpha subtype. J. Biol. Chem. 278, 46321-46328.
[18] van Pesch, V., Lanaya, H., Renauld, J.C., Michiels, T. 2004. Characterization of the murine alpha interferon gene family. J. Virol. 78, 8219-8228.
[19] Yerle, M., Gellin, J., Echard, G., Lefevre, F., Gillois, M. 1986. Chromosomal localization of leukocyte interferon gene in the pig (Sus scrofa domestica L.) by in situ hybridization. Cytogenet Cell Genet. 42,129-132.
[20] Lefevre, F. and La Bonnardiere, C. 1986. Molecular cloning and sequencing of a gene encoding biologically active porcine alpha-interferon. J Interferon Res. 6, 349-360.
[21] Lefevre, F., Mege, D., Haridon, R.L., Bernard, S., Vaureix, C.D., La Bonnardiere, C. 1990. Contribution of molecular biology to the study of the porcine interferon system. Vet. Microbiol. 23,245-257.
[22] Lefevre, F., Haridon, R.L., Cuesta, F.B., La Bonnardiere, C. 1990. Production, purification and biological properties of an Escherichia coli-derived recombinant porcine alpha interferon. J. Gen. Virol. 71,1057-1063.
[23] La Bonnardiere, C., Lefevre, F., Charley, B. 1994. Interferon response in pigs: molecular and biological aspects. Vet. Immunol. Immunopathol. 43,29-36.
[24] Cheng, G., Zhao, X., Yan W.Y., et al. 2007. Alpha interferon is a powerful adjuvant for a recombinant protein vaccine against foot-and-mouth disease virus in swine, and an effective stimulus of in vivo immune response. Vaccine 25,5199-5208.
[25] Chinsangaram, J., Piccone, M.E., Grubman, M.J. 1999. Ability of foot-and-mouth disease virus to form plaques in cell culture is associated with suppression of alpha/beta interferon. J. Virol. 73,9891-9898.
[26] Chinsangaram, J., Koster, M., Grubman, M.J. 2001. Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase. J. Virol. 75, 5498-5503.
[27] Chinsangaram, J., Moraes, M.P., Koster, M., Grubman, M.J. 2003. Novel viral disease control strategy: Adenovirus expressing alpha interferon rapidly protects porcine from foot-and-mouth disease. J. Virol. 77, 1621-1625.
[28] Valarcher, J.F., Furze, J., Wyld, S., Cook, R., Conzelmann, K.K., Taylor, G. 2003. Role of alpha/beta interferons in the attenuation and immunogenicity of recombinant bovine respiratory syncytial viruses lacking NS proteins. J. Virol. 77, 8426-8439.
[29] Moraes, M.P., Chinsangaram, J., Brum, M.C., Grubman, M.J. 2003. Immediate protection of porcine from foot-and-mouth disease: a combination of adenoviruses expressing interferon alpha and a foot-and-mouth disease virus subunit vaccine. Vaccine 22,268-279.
[30] Hughes, T.K., Chin, R., Tyring, S.K., Rady, P.L. 1994. Distinction of mouse interferon-alpha subtypes by polymerase chain-reaction utilizing consensus primers and type-specific oligonucleotide probes. J. Interf. Res. 14,117-120.
[31] Fung, M.C., Sia, S.F., Leung, K.N., Mak, N.K. 2004. Detection of differential expression of mouse interferon-alpha subtypes by polymerase chain reaction using specific primers. J. Immunol. Methods 284,177-186.
[32] Corpet, F. 1988. Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 16,10881-10890.
[33] Combet, C., Blanchet, C., Geourjon, C., Deleage, G. 2000. NPS@: network protein sequence analysis. Trends Biochem. Sci. 25,147-150.
[34] Thompson, J.D., Gibson, T.J., Plewniak, F., Jeanmougin, F., Higgins, D.G. 1997. The Clustal-X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 24, 4876-4882.
[35] Posada, D. and Crandall, K.A. 1998. MODELTEST: testing the model of DNA substitution. Bioinformatics 14, 817-818.
[36] Marc, R.R. and Dorothee, H. 2000. RRTree: Relative-Rate Tests between groups of sequences on a phylogenetic tree. Bioinformatics 16,296-297.
[37] Yang, Z. 2000. Phylogenetic analysis by maximun likelihood (PAML). Version 3.0. University College London, England.
[38] Pol, J.M., Broekhuysen-Davies J.M., Wagenaar F., La Bonnardiere C. 1991. The influence of porcine recombinant interferon-alpha 1 on pseudorabies virus infection of porcine nasal mucosa in vitro. J Gen. Virol. 72, 933-938.
[39] Braganca, J., Genin, P., Bandu, M.T., Darracq, N., Vignal, M., Casse, C., Doly, J., Civas, A. 1997. Synergism between multiple virus-induced factor-binding elements involved in the differential expression of interferon alpha genes. J. Biol. Chem. 272,22154-22162.
[40] Lin, R.T., Mamane, Y., Hiscott, J. 2000. Multiple regulatory domains control IRF-7 activity in response to virus infection. J. Biol. Chem. 275, 34320-34327.
[41] Juang, Y.T., Lowther, W., Kellum, M., Au, W.C., Lin, R., Hiscott, J., Pitha, P.M. 1998. Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc. Natl. Acad. Sci. U. S. A. 95, 9837-9842.
[42] Naf, D., Hardin, S.E, Weissmann, C. 1991. Multimerization of AAGTGA and GAAAGT generates sequences that mediate virus inducibility by mimicking an interferon promoter element. Proc. Natl. Acad. Sci. U. S. A. 88,1369-1373.
[43] Morin, P., Braganca, J., Bandu, M.T., Lin, R., Hiscott, J., Doly, J., Civas, A. 2002. Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription. J. Mol. Biol. 316,1009-1022.
[44] Radhakrishnan, R., Walter, L.J., Hruza, A., Reichert, P., Trotta, P.P., Nagabhushan, T.L., Walter, M.R. 1996. Zinc mediated dimer of human interferon-alpha (2b) revealed by X-ray crystallography. Structure 4, 1453-1463.
[45] Cheng G., Chen, W.Z., Li, Z.F., Yan, W.Y., Zhao, X., Xie, J., Liu, M.Q., Zhang, H., Zhong, Y. Zheng, Z.X. 2006. Characterization of the porcine alpha interferon multigene family. Gene 382,28-38.
[46] Force, A., Lynch, M., Pickett, F.B., Amores, A., Yan, Y.L., Postlethwait, J. 1999. Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151,1531-1545.
[47] Hibbert, L. and Foster, G.R. 1999. Human type I interferons differ greatly in their effects on the proliferation of primary B cells. J. Interf. Cytokine Res. 19, 309-318.
[48] Santodonato, L., Ferrantini, M., Palombo, F., Aurisicchio, L., Delmastro, P., La Monica, N., Di Marco, S., Ciliberto, G., Du, M.X., Taylor, M.W., Belardelli, F. 2001. Antitumor activity of recombinant adenoviral vectors expressing murine IFN-alpha in mice injected with metaSTATic IFN-resistant tumor cells. Cancer Gene Ther. 8, 63-72.
[49] Yeow, W.S., Lawson, C.M., Beilharz, M.W. 1998. Antiviral activities of individual murine IFN-alpha subtypes in vivo: intramuscular injection of IFN expression constructs reduces cytomegalovirus replication. J. Immunol. 160, 2932-2939.
[50] Larrea, E., Alberdi, A., Castelruiz, Y, Boya, P., Civeira, M.P., Prieto, J. 2001. Expression of interferon-alpha subtypes in peripheral mononuclear cells from patients with chronic hepatitis C: a role for interferon-alpha 5. J. Viral Hepatitis 8, 103-110.
[51] Wang, A.M., Doyle, M.V., Mark, D.F. 1989. Quantitation of mRNA by the polymerase chain reaction. Proc. Natl. Acad. Sci. U. S. A. 86,9717-9721.
[52] Gilliland, G., Perrin, S., Blanchard, K., Bunn, H.F. 1990. Analysis of cytokine messenger-RNA and DNA-detection and quantitation by competitive polymerase chain-reaction. Proc. Natl. Acad. Sci. U. S. A. 87,2725-2729.
[53] Babu, J.S., Kanangat, S., Rouse, B.T. 1993. Limitations and modifications of quantitative polymerase chain reaction-application to measurement of multiple messenger-RNAs present in small amounts of sample RNA. J. Immunol. Methods 165,207-216.
[54] Reiner, S.L., Zheng, S.C., Corry, D.B., Locksley, R.M. 1993. Constructing polycompetitor cDNAs for quantitative PCR. J. Immunol. Methods 165, 37-46.
[55] Kozbor, D., Hyjek, E., Wiaderkiewicz, R., Wang, Z., Wang, M., Loh, E. 1993. Competitor messenger-RNA fragments for quantitation of cytokine specific transcripts in cell lysates. Mol. Immunol. 30,1-7.
[56] Kamstrup, S., Verthelyi, D., Klinman, D.M. 2001. Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotides. Veterinary Microbiology 78,353-362.
[57] Johansson, E., Wallgren, P., Fuxler, L., Domeika, K., Lefevre, F., Fossum, C. 2002. The DNA vaccine vector pcDNA3 induces IFN-alpha production in pigs. Vet. Immunol. Immunopathol. 87,29-40.
[58] Magnusson, M., Johansson, E., Berg, M., Eloranta, M.L., Fuxler, L., Fossum, C. 2001. The plasmid pcDNA3 differentially induces production of interferon-alpha and interleukin-6 in cultures of porcine leukocytes. Vet. Immunol. Immunopathol. 78,45-56.
[1]Pestka,S.,Langer,J.A.,Zoon,K.C.,and Samuel,C.E.1987.Interferons and their actions.Annu.Rev.Biochem.56,727-777.
[2]Maeyer,E.,and Maeyer-Guignard,J.1998.The Cytokine Handbook (Thompson,A.,ed) 3rd Ed.,pp.491-516,Academic Press,San Diego,CA.
[3]LaFleur,D.W.,Nardelli,B.,Tsareva,T.,Mather,D.,Feng,P.,Semenuk,M.,Taylor,K.,Buergin,M.,Chinchilla,D.,Roshke,V.,Chen,G.,Ruben,S.M.,Pitha,P.M.,Coleman,T.A.,Moore,P.A.2001.Interferon-kappa,a novel type Ⅰinterferon expressed in human keratinocytes.J.Biol.Chem.276,39765-39771.
[4]Krausea,C.D.and Pestka,S.2005.Evolution of the Class 2 cytokines and receptors,and discovery of new friends and relatives.Pharmacology &Therapeutics 106,299-346.
[5]Pestka,S.,Krause,C.D.,Walter,M.R.2004.Interferons,interferon-like cytokines and their receptor.Immunological Reviews 202,8-32.
[6]Cheng,G.,Zhao,X.,Chen,W.Z.,Yah,W.Y.,Liu,M.Q.,Chen,J.,Zhao,X.Z.2007.Detection of Differential Expression of Porcine IFN-α Subtypes by Reverse Transcription Polymerase Chain Reaction.Journal of interferon and cytokine research 27,579-587.
[7]Demmers,K.J.,Derecka,K.,Flint,A.2001.Trophoblast interferon and pregnancy.Reproduction 121,41-49.
[8]Roberts,R.M.,Ealy,A.D.,Alexenko,A.P.,Han,C.S.,Ezashi,T.1999.Trophoblast interferons.Placenta 20,259-264.
[9] Nardelli, B., Zaritskaya, L., Semenuk, M., Cho, Y.H., La Fleur, D.W., Shah, D., Ullrich, S., Girolomoni, G., Albanesi, C., Moore, P.A. 2002. Regulatory effect of IFN-κ, A novel type I IFN, on cytokine production by cell of the innate immune system. J. Immunol. 169,4822-4830.
[10] Lefevre F, Guillomot M, D'Andrea S, Battegay S, La Bonnardiere C. 1998. Interferon-detla: the first member of a novel type I interferon family. Biochimie 80,779-788.
[11] Oritani, K., Medina, K.L., Tomiyama, Y., Ishikawa, J., Okajima, Y., Ogawa, M., Yokota, T., Aoyama, K., Takahashi, I., Kincade, P.W., Matsuzawa, Y. 2000. Limitin: an interferon-like cytokine that preferentially influences B lymphocyte precursors. Nat. Med. 6,659-666.
[12] Oritani, K., Kincade, P.W., Zhang, C., Tomiyama, Y., Matsuzawa, Y. 2001. Type I interferons and limitin: a comparison of structures, receptors, and functions. Cytokine & Growth Factor Rev. 12,337-348.
[13] Cavalieri, R.L., Havell, E.A., Vileck, J., Pestka, S. 1977. Induction and decay of human fibroblast interferon mRNA. Proc. Natl. Acad. Sci. U. S. A. 74, 4415-4419.
[14] Raj, N.B., and Pitha, P.M. 1983. Two levels of regulation of beta-interferon gene expression in human cells. Proc. Natl. Acad. Sci. U. S. A. 80,3923-3927.
[15] Uze, G., Lutfalla, G., Gresser, I. 1990. Knockout and reconstitution of a functional human type I interferon receptor complex. Cell 60,225-234.
[16] Soh, J., Mariano, T.M., Lim, J.K., Izotova, L., Mirochnitchenko, O., Schwartz, B., Langer, J.A., Pestka, S. 1994. Expression of a functional human type I interferon receptor in hamster cells: application of functional yeast artificial chromosome (YAC) screening. J. Biol. Chem. 269,18102-18110.
[17] Domanski, P., Witte, M., Kellum, M., Rubinstein, M., Hackett, R., Pitha, P., Colamonici, O.R. 1995. Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J. Biol. Chem. 270,21606-21611.
[18] Pestka, S. 1997. The interferon receptors. Semin. Oncol. 24, S9.
[19] Stark, G.R., Kerr, I.M., Williams, B.R., Silverman, R.H., Schreiber, R.D. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67,227-264.
[20] Schindler, C, and Darnell, J.E. 1995. Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Ann. Rev. Biochem. 64,621-651.
[21] Stark, G.R., Kerr, I.M., Williams, B.R., Silverman, R.H., Schreiber, R.D. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67,227-264.
[22] Gutterman, J.U. 1994. Cytokine therapeutics: lessons from interferon alpha. Proc. Natl. Acad. Sci. U. S. A. 91,1198-1205.
[23] Schultz, J., Milpetz, F., Bork, P., Ponting, C.P. 1998. SMART, a simple modular architecture research tool: Identification of signaling domains. Proc. Natl. Acad. Sci. U. S. A. 95,5857-5864.
[24] Letunic, I., Copley, R.R., Pils, B., Pinkert, S., Schultz, J., Bork, P. 2006. SMART 5: domains in the context of genomes and networks. Nucleic Acids Research 34, D257-D260.
[25] Lefevre, R, Guillomot, M., D'Andrea, S., Battegay, S., La Bonnardiere, C. 1998. Interferon-detla: the first member of a novel type I interferon family. Biochimie 80, 779-788.
[26] Kotenko, S.V., Gallagher, G., Baurin, V.V., Lewis-Antes, A., Shen, M., Shah, N.K., Langer, J.A., Sheikh, R, Dickensheets, H., Donnelly, R.P. 2003. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat. Immunol. 4,69-77.
[27] Quadt-Akabayov, S.R., Chill, J.H., Levy, R., Kessler, N., Anglister J. 2006. Determination of the human type I interferon receptor binding site on human interferon-a2 by cross saturation and an NMR-based model of the complex. Protein Science 15,2656-2668.
[28] Chill, J.H., Nivasch, R., Levy,R., Albeck, S., Schreiber, G., Anglister, J. 2002. The human interferon receptor: NMR-Based modeling, mapping of the IFN-R2 binding site, and observed Ligand-Induced tightening. Biochemistry 41,3575-3585.
[29] Chill, J.H., Quadt, S.R., Levy, R., Schreiber, G., Anglister, J. 2003. The Human Type I Interferon Receptor: NMR Structure Reveals the Molecular Basis of Ligand Binding. Structure 11, 791-802.
[30] Torrence, P.F. et al. 1985. How interferon works. In Biological response modifiers. pp. 77-119, Orlando: Academic Press.
[31] Sandberg, K., Eloranta, M.L., Campbell, I.L. 1994. Expression of alpha/beta interferons and their relationship to IFN-alpha/beta-induced genes in lymphocytic choriomeningitis. J Virol. 68, 7358-7366.
[32] McDowell, M.A., Lucas, D.M., Nicolet, C.M., Paulnock, D.M. 1995. Differential utilization of IFN-responsive element in two maturationally distinct Macrophage cell lines.J.lmmunol.155,4933-4941.
[33]Le Bon,A.,Tough,D.F.2002.Links between innate and adaptive immunity via type Ⅰ interferon.Current Opinion in Immunology.14,432-436.
[34]Alexopoulou,L.,Holt,A.C.,Medzhitov,R.,Flavell,R.A.2001.Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3.Nature 413,732-738.
[35]Milone,M.C.and Fitzgerald-Bocarsly,P.1998.The mannose receptor mediates induction of interferon-alpha in peripheral blood dendritic cells by enveloped RNA and DNA viruses.J.Immunol.161,2391-2399.
[1] Belsham, G.J. 1993. Distinctive features of foot-and-disease virus, a member of the picornavirus family-aspects of virus protein-synthesis, protein processing and structure. Prog. Biophys. Mol. Biol. 60,241-260.
[2] Pereira, H.G. 1981. Foot-and-mouth disease. In: Gibbs EPJ, editor. Virus Diseases of Food Animals. pp. 333-363, London, Academic Press Inc.
[3] Barteling, S.J. and Vreeswijk, J. 1991. Developments in foot-and-mouth-disease vaccines. Vaccine 9, 75-88.
[4] Baxt, B., Morgan, D.O., Roberton, B.H., Timpone, C.A. 1984. Epitopes on foot-and-mouth disease virus outer capsid protein VP1 involved in neutralization and cell attachment. J Virol. 51,298-305.
[5] Collen, T., Dimarchi, R., Doel, T.R. 1991. A T-cell epitope in VP1 of foot-and-mouth-disease virus is immunodominant for vaccinated cattle. J Immunol. 146, 749-755.
[6] Strohmaier, K., Franze, R., Adam, K.H. 1982. Location and characterization of the antigenic portion of the FMDV immunizing protein. J Gen. Virol. 59, 295-306.
[7] Li, G.J., Chen, W.Z., Yan, W.Y., Zhao, K., Liu, M.Q., Zhang, J., Fei, L., Xu, Q.X., Sheng, Z.T., Lu, Y.G., Zheng, Z.X. 2004. Comparison of immune responses against foot-and-mouth disease virus induced by fusion proteins using the swine IgG heavy chain constant region or beta-galactosidase as a carrier of immunogenic epitopes. Virology 328,274-281.
[8] Le Bon, A., Schiavoni, G., D'Agostino, G., Gresser, I., Belardelli, F., Tough, D.F. 2001. Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14, 461-470.
[9] Braun, D., Caramalho, I., Demengeot, J. 2002. IFN-alpha/beta enhances BCR-dependent B cell responses. Int. Immunol. 14,411-419.
[10] Hunter, C.A., Gabriel, K.E., Radzanowski, T., Neyer, L.E., Remington, J.S. 1997. Type I interferons enhance production of IFN-gamma by NK cells. Immunol. Lett. 59,1-5.
[11] Tough, D.F., Borrow, P., Sprent, J. 1996. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947-1950.
[12] Marrack, P., Kapoler, J., Mitchell, T. 1999. Type I interferons keep activated T cells alive. J Exp. Med. 189,521-529.
[13] Nistico, P., Tecce, P., Giacomini, P., Cavallari, A., Dagnano, I., Fisher, P.B., Natali, P.G. 1990. Effect of recombinant human-leukocyte, fibroblast, and immune interferons on expression of class-I and class-II major histocompatibilty complex and invariant chain in early passage human-melanoma cells. Cancer Res. 50,7422-7429.
[14] Luft, T., Pang, K.C., Thomas, E., Hertzog, P., Hart, D.N.J., Trapani, J., Cebon, J. 1998. Type I IFNs enhance the terminal differentiation of dendritic cells. J Immunol. 161,1947-1953.
[15] Montoya, M., Schiavoni, G., Mattei, F., Gresser, I., Belardelli, F., Borrow, P., Tough, D.F. 2002. Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99,3263-3271.
[16] Santini, S.M., Lapenta, C, Logozzi, M., Parlato, S., Spada, M., Di Pucchio, T., Belardelli, F. 2000. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp. Med. 191,1777-1788.
[17] Taylor, J.L. and Grossberg, S.E. 1998. The effects of interferon-alpha on the production and action of other cytokines. Semin. Oncol. 25,23-29.
[18] Mitani, Y, Takaoka, A., Kim, S.H, Kato, Y., Yokachi, T., Tanaka, N., Taniguchi, T. 2001. Cross talk of the interferon-alpha/beta signaling complex with gp130 for effective interleukin-6 signaling. Genes to cells 6,631-640.
[19] Takaoka, A., Mitani, Y., Suemori, H., Sato, M., Yokochi, T., Noguchi, S., Tanaka, N., Taniguchi, T. 2000. Cross talk between interferon-gamma and -alpha/-beta signaling components in caveolar membrane domains. Science 288,2357-2360.
[20] Biron, C.A. 1998. Role of early cytokines, including alpha and beta interferons (IFN-alpha/beta), in innate and adaptive immune responses to viral infections. Seminars in immunology 10,383-390.
[21] Proietti, E., Bracci, L., Puzelli, S., Di Pucchio, T., Sestili, P., De Vincenzi, E., Venditti, M., Capone, I., Seif, I., De Maeyer, E., Tough, D., Donatelli, I., Belardelli, F. 2002. Type I IFN as a natural adjuvant for a protective immune response: Lessons from the influenza vaccine model. J Immunol. 169, 375-383.
[22] Bracci, L., Canini, I., Puzelli, S., Sestili, P., Venditti, M., Spada, M., Donatelli, I., Belardelli, F., Proietti, E. 2005. Type I IFN is a powerful mucosal adjuvant for a selective intranasal vaccination against influenza virus in mice and affects antigen capture at mucosal level. Vaccine 23,2994-3004.
[23] de Avila Botton, S., Brum, M.C.S., Bautista, E., Koster, M., Weiblen, R., Golde, W.T., Grubman, M.J. 2006. Immunopotentiation of a foot-and-mouth disease virus subunit vaccine by interferon alpha. Vaccine 24, 3446-3456.
[24] Cheng, G., Chen, W.Z., Li, Z.F., Yan, W.Y., Zhao, X., Xie, J., Liu, M.Q., Zhang, H., Zhong, Y., Zheng, Z.X. 2006. Characterization of the porcine alpha interferon multigene family. Gene 382,28-38.
[25] Kirby, C. and Gregoriadis, G. 1984. Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes. Biotechnology 11, 979-984.
[26] Golding, S.M., Hedger, R.S., Talbot, P. 1976. Radial immuno-diffusion and serum-neutralisation techniques for the assay of antibodies to swine vesicular disease. Res. Vet. Sci. 20,142-147.
[27] Kang, Y.M., Jin, H., Zheng, G.X., Xie, Q.F., Yin, J.M., Yu, Y., Xiao, C., Zhang, X.Y., Chen, A.S., Wang, B. 2005. The adjuvant effect of levamisole on killed viral vaccines. Vaccine 23, 5543-5550.
[28] Maghni, K., Nicolescu, O.M., Martin, J.G. 1999. Suitability of cell metabolic colorimetric assays for assessment of CD4~+ T cell proliferation: comparison to 5-bromo-2-deoxyuridine (BrdU) ELISA. Journal of Immunological Methods 223,185-194.
[29] Barnett, P.V., Cox, S.J., Aggarwal, N., Gerber, H., McCullough, K.C. 2002. Further studies on the early protective responses in pigs following immunisation with high potency foot-and-mouth disease vaccine. Vaccine 20, 3197-3208.
[30] Sun, T., Lu, P., Wang, X. 2004. Localization of infection-related epitopes on the non-structural protein 3ABC of foot-and-mouth disease virus and the application of tandem epitopes. J Virol. Methods 119, 79-86.
[31] Isaacs, A., and Lindenmann, J. 1957. Virus interference: the interferon. Proc. R. Soc. Med. 147,258-267.
[32] Dalpke, A., Zimmermann, S., Heeg, K. 2002. Immunopharmacology of CpG DNA. Biol. Chem. 383, 1491-1500.
[33] Cox, J.C. and Coulter, A.R. 1997. Adjuvants-a classification and review of their modes of action. Vaccine 15,248-256.
[34] Falcone, M. and Sarvetnick, N. 1999. Cytokines that regulate autoimmune responses. Current Opinion in Immunology 11,670-676.
[35] King, C, Davies, J., Mueller, R., Lee, M.S., Krahl, T., Yeung, B., O'Connor, E., Sarvetnick, N. 1998. TGF-betal alters APC preference, polarizing islet antigen responses toward a Th2 phenotype. Immunity 8,601-613.
[36] Mueller, R., Bradley, L.M., Krahl, T., Sarvetnick, N. 1997. Mechanism underlying counterregulation of autoimmune diabetes by IL-4. Immunity 7, 411-418.
[37] Morgan, H, Bjorn, F.L., Michael, S.K., Daniel, S.C., Mark, M.D. 2006. T cells use two directionally distinct pathways for cytokine secretion. Nature Immunology 7,247-255.
[38] Lucey, D.R., Clerici, M., Shearer, G.M. 1996. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clinical Microbiology Reviews 9,532.
[39] So, E.Y., Park, H.H., Lee, C.E. 2000. IFN-gamma and IFN-alpha posttranscriptionally down-regulate the IL-4-induced IL-4 receptor gene expression. The Journal of Immunology 165, 5472-5479.
[40] Chinsangaram, J., Koster, M., Grubman, M.J. 2001. Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase. J Virol. 75, 5498-5503.
[41] de los Santos, T., Botton, S.D., Weiblen, R., Grubman, M.J. 2006. The leader proteinase of foot-and-mouth disease virus inhibits the induction of beta interferon mRNA and blocks the host innate immune response. J Virol. 80, 1906-1914.
[2]Pestka,S.,Krause,C.D.,Walter,M.R.2004.Interferon,interferon-like cytokines,and their receptors.Immunological Reviews 202,8-32.
[3]Sen,G.C.and Lengyel,P.1992.The interferon system.A bird's eye view of its biochemistry.J.Biol.Chem.267,5017-5020.
[4]Jin,B.Q.2001.Cellular and molecular immunology[M].pp.131-239,Beijing:Science Press.(In Chinese)
[5]Huising,M.O.,Kruiswijk,C.P.,Flik,G.2006.Phylogeny and evolution of class-Ⅰ helical cytokines.Journal of Endocrinology 189,1-25.
[6]Pestka,S.,Krause,C.D.,Sarkar,D.,Walter,M.R.,Shi,Y.F.,Fisher,P.B.2004.Interleukin-10 and related cytokines and receptors.Annu.Rev.Immunol.22,929-979.
[7]Krausea,C.D.and Pestka,S.2005.Evolution of the Class 2 cytokines and receptors,and discovery of new friends and relatives.Pharmacology &Therapeutics 106,299-346.
[8]Bazan,J.F.1990.Structural design and molecular evolution of a cytokine receptor superfamily.Proc.Natl.Acad.Sci.U.S.A.87,6934-6938.
[9]Thoreau,E.,Petridou,B.,Kelly,P.A.,Djiane,J.,Mornon,J.P.1991.Structural symmetry of the extracellular domain of the cytokine/growth hormone/prolactin receptor family and interferon receptors revealed by hydrophobic cluster analysis.FEBS Letters 282,26-31.
[10]Langer,J.A.,Cutrone,E.C.,Kotenko,S.2004.The class Ⅱ cytokine receptor (CRF2) family:overview and patterns of receptor-ligand interactions.Cytokine Growth Factor Rev.15,33-48.
[11]Sidney,P.,et al.1981.Defination and classification of the interferon.In: Methodsin Enzymology, Vol. 78, pp. 3-28, New York: Academic Press.
[12] Pestka, S., Langer, J.A., Zoon, K.C., Samuel, C.E. 1987. Interferons and their actions. Ann. Rev. Biochem. 56,727-777.
[13] Goeddel, D.V., Leung, D.W., Dull, T.J., Gross, M., Lawn, R.M., Mccandliss, R., Seeburg, P.H., Ullrich, A., Yelverton, E., Gray, P.W. 1981. The structure of eight distinct cloned human leukocyte interferon cDNA. Nature 290,20-26.
[14] Lengyel, P. 1982. Biochemistry of interferon and their actions. Ann. Rev. Biochem. 51,251-282.
[15] Ealick, S.E., Cook, W.J., Vijaykumar, S., Carson, M., Nagabhushan, T.L., Trotta, P.P., Bugg, C.E. 1991. Three-dimensional structure of recombinant human interferon-γ. Science 252, 698-702.
[16] Fish, E.N., Banerjee, K., Stebbing, N., 1989. The role of 3 domains in the biological-activity of human interferon-alpha. J Interferon Res. 9,97-114.
[17] Seto, M.H., Harkins, R.N., Adler, M., Whitlow, M, Church, W.B., Croze, E. 1995. Homology model of human interferon-a8 and its receptor complex. Protein Sci. 4,655-670.
[18] Yip,Y.K., Barrowclough, B.S., Urban, C, Vilcek, J. 1982. Molecular weight of human gamma interferon is similar to that of other human interferons. Science 215,411-413.
[19] Sareneva, T., Mortz, E., Tolo, H., Roepstorff, P., Julkunen, T. 1996 Biosynthesis and N-glycosylation of human interferon-gamma-Asn25 and Asn97 differ markedly in how efficiently they are glycosylated and in their oligosaccharide composition. Eur. J. Biochem. 242,191-200.
[20] Lefevre, F., Guillomot, M., D'Andrea, S., Battegay, S., La Bonnardiere, C. 1998. Interferon-detla: the first member of a novel type I interferon family. Biochimie 80,779-788.
[21] Roberts, R.M., Cross, J.C., Leaman, D.W. 1991. Unique features of the trophoblast interferons. Pharmacol. Ther. 51, 329-345.
[22] Oritani, K., Medina, K.L., Tomiyama, Y, Ishikawa, J., Okajima, Y, Ogawa, M., Yokota, T., Aoyama, K., Takahashi, I., Kincade, P.W., Matsuzawa, Y 2000. Limitin: an interferon-like cytokine that preferentially influences B lymphocyte precursors. Nat. Med. 6,659-666.
[23] van Pesch, V., Lanaya, H., Renauld, J.C., Michiels, T. 2004. Characterization of the murine alpha interferon gene family. Journal of virology 78, 8219-8228.
[24] Cheng, G., Chen, W.Z., Li, Z.F., Yan, W.Y., Zhao, X., Xie, J., Liu, M.Q., Zhang, H., Zhong, Y., Zheng, Z.X. 2006. Characterization of the porcine alpha interferon multigene family. Gene 382,28-38.
[25] Hardy, M.P., Owczarek, C.M., Jermiin, L.S., Ejdeback, M., Hertzog, P.J. 2004. Characterization of the type I interferon locus and identification of novel genes. Genomics 84,331-345.
[26] Adolf, G.R., Fruhbeis, B., Hauptmann, R., Kalsner, I., Maurerfogy, I., Ostermann, E., Patzelt, E., Schwendenwein, R., Sommergruber, W., Zophel, A. 1991. Human interferon omega 1: isolation of the gene, expression in Chinese hamster ovary cells and characterization of the recombinant protein. Biochim. et. Biophys. Acta 1089,167-174.
[27] Chen, J, Wood, W.I. 2003. Interferon PRO655. pp. 1-37, Genentech. [US 6,300,475] [Patent].
[28] Oritani, K., Kincade, P.W., Zhang, C., Tomiyama, Y., Matsuzawa, Y. 2001. Type I interferons and limitin: a comparison of structures, receptors, and functions. Cytokine & Growth Factor Rev. 12, 337-348.
[29] LaFleur, D.W., Nardelli, B., Tsareva, T., et al. 2001. IFN-κ, a novel type I interferon expressed in human keratinocytes. J. Biol. Chem. 276, 39765-39771.
[30] Nardelli, B., Zaritskaya, L., Semenuk, M., Cho, Y.H., La Fleur, D.W., Shah, D., Ullrich, S., Girolomoni, G., Albanesi, C., Moore, P.A. 2002. Regulatory effect of IFN-κ, A novel type I IFN, on cytokine production by cell of the innate immune system. J. Immunol. 169,4822-4830.
[31] Demmers, K.J., Derecka, K., Flint, A. 2001. Trophoblast interferon and pregnancy. Reproduction 121,41-49.
[32] Roberts, R.M., Ealy, A.D., Alexenko, A.P., Han, C.S., Ezashi, T. 1999. Trophoblast interferons. Placenta 20,259-264.
[33] Kotenko, S.V., Gallagher, G., Baurin, V.V., Lewis-Antes, A., Shen, M., Shah, N.K., Langer, J.A., Sheikh, F., Dickensheets, H., Donnelly, R.P. 2003. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat. Immunol. 4, 69-77.
[34] Sheppard, P, Kindsvogel, W., Xu, W.F., et al. 2003. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nat. Immunol. 4, 63-68.
[35] Stark, G.R., Kerr, I.M., Williams, B.R., Silverman, R.H., Schreiber, R.D. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67,227-264.
[36] Pestka, S., Kotenko, S.V., Muthukumaran, G., Izotova, L., Cook, J.R., Garotta, G. 1997. The interferon γ(IFN-γ) receptor: a paradigm for the multichain cytokine receptor. Cytokine Growth Factor Rev. 8,189-206.
[37] Pestka, S. 1997. The interferon receptors. Semin. Oncol. 24, S9.
[38] Uze, G., Lutfalla, G., Gresser, I. 1990. Genetic transfer of a functional human interferon a receptor into mouse cells: cloning and expression of its cDNA. Cell 60,225-234.
[39] Darnell, J.E. Jr. 1997. STATs and gene regulation. Science 277,1630-1635.
[40] Schindler, C., Fu, X.Y., Improta, T., Aebersold, R., Darnell, J.E. Jr. 1992. Proteins of transcription factor ISGF-3: one gene encodes the 91-and 84-kDa ISGF-3 proteins that are activated by interferon alpha. Proc. Natl. Acad. Sci. U. S. A. 89,7836-7839.
[41] Fu, X.Y., Schindler, C., Improta, T, Aebersold, R., Darnell, J.E. Jr. 1992. The roteins of ISGF-3, the interferon alpha-induced transcriptional activator, define a gene family involved in signal transduction. Proc. Natl. Acad. Sci. U. S. A. 89, 7840-7843.
[42] Nguyen, K.B., Watford, W.T., Salomon, R., Hofmann, S.R., Pien, G.C., Morinobu, A., Gadina, M., O'Shea, J.J., Biron, C.A. 2002. Critical role for STAT4 activation by type 1 interferons in the interferon-gamma response to viral infection. Science 297,2063-2066.
[43] Su, L. and David, M. 2000. Distinct mechanisms of STAT phosphorylation via the interferon-alpha/ beta receptor. Selective inhibition of STAT3 and STAT5 by piceatannol. J Biol. Chem. 275,12661-12666.
[44] Soh, J., Donnelly, R.J., Kotenko, S., Mariano, T.M., Cook, J.R., Wang, N., Emanuel, S., Schwartz, B., Miki, T., Pestka, S. 1994. Identification and sequence of an accessory factor required for activation of the human interferon-gamma receptor. Cell 76, 793-802.
[45] Hemmi, S., Bohni, R., Stark, G., Di Marco, F., Aguet, M. 1994. A novel member of the interferon receptor family complements functionality of the murine interferon gamma receptor in human cells. Cell 76, 803-810.
[46] Shuai, K., Schindler, C., Prezioso, V.R., Darnell, J.E. Jr. 1992. Activation of transcription by IFN-gamma: tyrosine phosphorylation of a 91-kD DNA binding protein. Science 258,1808-1812.
[47] Shuai, K., Stark, G.R., Kerr, I.M., Darnell, J.E. Jr. 1993. A single phosphotyrosine residue of STAT91 required for gene activation by interferon-gamma. Science 261, 1744-1746.
[48] Durbin, J.E., Hackenmiller, R., Simon, M.C., Levy, D.E. 1996. Targeted disruption of the mouse STAT1 gene results in compromised innate immunity to viral disease. Cell 84,443-450.
[49] Eilers, A. and Decker, T. 1995. Activity of STAT family transcription factors is developmentally controlled in cells of the macrophage lineage. Immunobiology 193, 328-333.
[50] Krause, C.D., Mei, E.W, Xie, J.X., Jia, Y.W, Bopp, M.A., Hochstrasser, R.M., Pestka, S. 2002. Seeing the light: preassembly and ligand-induced changes of the interferon gamma receptor complex in cells. Mol. Cell. Proteomics 1, 805-815.
[51] David, M. 2002. Signal transduction by type I interferons. Biotechniques Suppl. 58-65.
[52] Takaoka, A., Hayakawa, S., Yanai, H., Stoiber, D., Negishi, H., Kikuchi, H., Sasaki, S., Imai, K., Shibue, T., Honda, K., Taniguchi, T. 2003. Integration of interferonalpha/ beta signalling to p53 responses in tumour suppression and antiviral defence. Nature 424, 516-523.
[53] Abramovich, C., Yakobson, B., Chebath, J., Revel, M. 1997. A protein-arginine methyltransferase binds to the intracytoplasmic domain of the IFNAR1 chain in the type I interferon receptor. EMBO J 16, 260-266.
[54] Chung, C.D., Liao, J.Y., Liu, B., Rao, X.P., Jay, P., Berta, P., Shuai, K. 1997. Specific inhibition of STAT3 signal transduction by PIAS3. Science 278, 1803-1805.
[55] Kile, B.T., Schulman, B.A., Alexander, W.S., Nicola, N.A., Martin, H.M., Hilton, D.J. 2002. The SOCS box: a tale of destruction and degradation. Trends Biochem. Sci. 27,235-241.
[56] Kim, T.K. and Maniatis, T. 1996. Regulation of interferon-gamma-activated STATl by the ubiquitin-proteasome pathway. Science 273,1717-1719.
[57] Radhakrishnan, R., Walter, L.J., Hruza, A., Reichert, P., Trotta, P.P., Nagabhushan, T.L., Walter, M.R. 1996. Zinc mediated dimer of human interferon-alpha2b revealed by X-ray crystallography. Structure 4,1453-1463.
[58] Klaus, W., Gsell, B., Labhardt, A.M., Wipf, B., Senn, H. 1997. The three-dimensional high resolution structure of human interferon alpha-2a determined by heteronuclear NMR spectroscopy in solution. J Mol. Biol. 274, 661-675.
[59] Karpusas, M., Nolte, M., Benton, C.B., Meier, W., Lipscomb, W.N., Goelz, S. 1997. The crystal structure of human interferon beta at 2.2-A° resolution. Proc. Natl.Acad. Sci. U. S.A. 94,11813-11818.
[60] Radhakrishnan, R., Walter, L.J., Subramaniam, P.S., Johnson, H.M., Walter, M.R. 1999. Crystal structure of ovine interferon-tau at 2.1 A° resolution. J Mol. Biol. 286, 151-162.
[61] Walter, M.R, Windsor, W, Nagabhushan, T.L, Lundell, D.J, Lunn, C.A., Zauodny, P.J., Narula, S.K. 1995. Crystal structure of a complex between interferon-gamma and its soluble high-affinity receptor. Nature 376,230-235.
[62] Thiel, D.J, le Du, M.H, Walter, R.L, D'Arcy, A, Chene, C, Fountoulakis, M, Garotta, G, Winkler, F.K, Ealick, S.E. 2000. Observation of an unexpected third receptor molecule in the crystal structure of human interferon-gamma receptor complex. Structure Fold Des. 8,927-936.
[63] Randal, M. and Kossiakoff, A.A. 2001. The structure and activity of a monomeric interferon-gamma: alpha-chain receptor signaling complex. Structure (Camb) 9,155-163.
[64] Rubinstein, M, Rubinstein, S, Familletti, P.C., Miller, R.S, Waldman, A.A. 1978. Human leukocyte interferon purified to homogeneity. Science 202, 1289-1290.
[65] Pestka, S. 1983. The human interferons-from protein purification and sequence to cloning and expression in bacteria: before, between, beyond. Arch. Biochem. Biophys. 221, 1-37.
[66] Pestka, S. 2000. The human interferon alpha species and receptors. Biopolymers 55,254-287.
[67] Evinger, M., Rubinstein, M., Pestka, S. 1981. Antiproliferative and antiviral activities of human leukocyte interferons. Arch. Biochem. Biophys. 210, 319-329.
[68] Pestka, S. 1997. The human interferon-alpha species and hybrid proteins. Semin. Oncol. 24, S9.
[69] Ortaldo, J.R. Herberman, R.B, Harvey, C., Osheroff, P, Pan, Y.C.E., Kelder, B, Pestka, S. 1984. A species of human alpha interferon that lacks the ability to boost human natural killer activity. Proc. Natl. Acad. Sci. U. S. A. 81, 4926-4929.
[70] Ortaldo, J.R., et al. 1983. Augmentation of NK activity with recombinant and hybrid recombinant human leukocyte interferons. In: De Maeyer E, Schellekens H, eds. The Biology of the Interferon System. pp. 353-358, Amsterdam: Elsevier Science Publishers.
[71] van Pesch, V. and Michiels, T. 2003. Characterization of interferon-alpha 13, a novel constitutive murine interferon-alpha subtype. J. Biol. Chem. 278, 46321-46328.
[72] Nguyen, H., Hiscott, J., Pitha, P. M. 1997. The growing family of interferon regulatory factors. Cytokine Growth Factor Rev. 8,293-312.
[73] Mamane, Y., Heylbroeck, C., Genin, P., Algarte, M., Servant, M.J., LePage, C., De Luca, C., Kwon, H., Lin, R.T., Hiscott, J. 1999. Interferon regulatory factors: the next generation. Gene 237,1-14.
[74] Taniguchi, T., Tanaka, N., Ogasawara, K., Taki, S., Sato, M., Takaoka, A. 2000. The transcription factor IRF-1 and its family members in the regulation of host defense. Cold Spring Harb. Symp. Quant. Biol. 64,465-472.
[75] Taniguchi, T., Ogasawara, K., Takaoka, A. Tanaka, N. 2001. IRF family of transcription factors as the regulators of host defense. Annu. Rev. Immunol. 19, 623-655.
[76] Lin, R., Mamane, Y. Hiscott, J. 2000. Multiple regulatory domains control IRF-7 activity in response to virus infection. J. Biol. Chem. 275, 34320-34327.
[77] Yeow, W. S., Au, W.C., Juang, Y.T, Fields, C.D., Dent, C.L., Gewert, D.R., Pitha, P.M. 2000. Reconstitution of virus-mediated expression of interferon alpha genes in human fibroblast cells by ectopic interferon regulatory factor-7. J. Biol. Chem. 275,6313-6320.
[78] Sato, M., Suemori, H., Hata, N., Asagiri, M., Ogasawara, K., Nakao, K., Nakaya, T., Katsuki, M., Noguchi, S., Tanaka, N., Taniguchi, T. 2000. Distinct and essential roles of transcription factors IRF-3 and IRF-7 in response to viruses for IFN-α/β gene induction. Immunity 13, 539-548.
[79] Braganca, J., Genin, P., Bandu, M.T., Darracq, N., Vignal, R., Casse, C., Doly, J., Civas, A. 1997. Synergism between multiple virus-induced factor binding elements involved in the differential expression of interferon alpha genes. J. Biol. Chem. 272,22154-22162.
[80] Lin, R.T., Mamane, Y., Hiscott, J. 2000. Multiple regulatory domains control IRF-7 activity in response to virus infection. J. Biol. Chem. 275, 34320-34327.
[81] Juang, Y.T., Lowther, W., Kellum, M., Au, W.C., Lin, R., Hiscott, J., Pitha, P.M. 1998. Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc. Natl. Acad. Sci. U. S. A. 95, 9837-9842.
[82] Morin, P., Braganca, J., Bandu, M.T., Lin, R., Hiscott, J., Doly, J., Civas, A. 2002. Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription. J. Mol. Biol. 316,1009-1022.
[83] Torrence, P.F. et al. 1985. How interferon works. In Biological response modifiers. pp. 77-119, Orlando: Academic Press.
[84] Sandberg, K., Eloranta, M.L., Campbell, I.L. 1994. Expression of alpha/beta interferons and their relationship to IFN-alpha/beta-induced genes in lymphocytic choriomeningitis. J. Virol. 68,7358-7366.
[85] McDowell, M.A., Lucas, D.M., Nicolet, C.M., Paulnock, D.M. 1995. Differential utilization of IFN-responsive element in two maturationally distinct Macrophage cell lines. J. Immunol. 155,4933-4941.
[86] Muller, U., Steinhoff, U., Reis, L.F.L., Hemmi, S., Pavlovic, J., Zinkernagel, R.M., Aguet, M. 1994. Functional role of type I and type II interferons in antiviral defense. Science 264,1918-1921.
[87] Kaiser, P., Wain, H.M., Rothwell, L. 1998. Structure of the chicken interferon-g gene, and comparison to mammalian homologues. Gene 207, 25-32.
[88] Altmann, S.M., Mellon, M.T., Distel, D.L., Kim, C.H. 2003. Molecular and functional analysis of an interferon gene from the zebrafish, Danio rerio. J Virol. 77,1992-2002.
[89] Lutfalla, G., Crollius, H.R., Stange-thomann, N., Jaillon, O., Mogensen, K., Monneron, D. 2003. Comparative genomic analysis reveals independent expansion of a lineage-specific gene family in vertebrates: The class II cytokine receptors and their ligands in mammals and fish. BMC Genomics 4, 1-15.
[90] Robertsen, B., Bergan, V, Rokenes, T., Larsen, R., Albuquerque, A. 2003. Atlantic salmon interferon genes: cloning, sequence analysis, expression, and biological activity. J Interferon Cytokine Res. 23, 601-612.
[91] Sick, C, Schultz, U., Staeheli, P. 1996. A family of genes coding for two serologically distinct chicken interferons. J. Biol. Chem. 271,7635-7639.
[92] Nanda, I., Sick, C., Munster, U., Kaspers, B., Schartl, M., Staeheli, P., Schmid, M. 1998. Sex chromosome linkage of chicken and duck type I interferon genes: further evidence of evolutionary conservation of the Z chromosome in birds. Chromosoma 107,204-210.
[93] Staeheli, P., Puehler, F., Schneider, K., Gobel, T.W., Kaspers, B. 2001. Cytokines of birds: conserved functions-a largely different look. J Interferon Cytokine Res. 21,993-1010.
[94] Harrison, G.A., Young, L.J., Watson, C.M., Miska, K.B., Miller, R.D., Deane, E.M. 2003. A survey of type I interferons from a marsupial and monotreme: implications for the evolution of the type I interferon gene family in mammals. Cytokine 21,105-119.
[95] Park, C., Li, S., Cha, E., Schindler, C. 2000. Immune response in STAT2 knockout mice. Immunity 13, 795-804.
[96] Roberts, R.M., Ezashi, T., Rosenfeld, C.S., Ealy, A.D., Kubisch, H.M. 2003. Evolution of the interferon tau genes and their promoters, and maternal-trophoblast interactions in control of their expression. Reproduction Suppl. 61,239-251.
[97] Pestka, S., Kelder, B., Familletti, P.C., Moschera, J.A., Crowl, R., Kempner, E.S. 1983. Molecular weight of the functional unit of human leukocyte, fibroblast, and immune interferons. J. Biol. Chem. 258,9706-9709.
[98] Igawa, D., Sakai, M., Savan, R. 2006. An unexpected discovery of two interferon gamma-like genes along with interleukin (IL)-22 and -26 from teleost: IL-22 and -26 genes have been described for the first time outside mammals. Molecular Immunology 43, 999-1000.
[99] Taya, Y., Devos, R., Tavernier, J., Cheroutre, H., Engler, G, Fiers, W. 1982. Cloning and structure of the human immune interferon-gamma chromosomal gene. EMBO J 1,953-958.
[100] Gray, P.W. and Goeddel, D.V. 1982. Structure of the human immune interferon gene. Nature 298, 859-863.
[101] Suresh, M., Karaca, K., Foster, D., Sharma, J.M. 1995. Molecular and functional characterization of turkey interferon. J. Virol. 69, 8159-8163.
[102] Schultz, U., Kock, J., Schlicht, H.J., Staeheli, P. 1995. Recombinant duck interferon: a new reagent for studying the mode of interferon action against hepatitis B virus. Virology 212,641-649.
[103] Heller, E.D., Levy, A.M., Vaiman, R., Schwartsburd, B. 1997. Chicken-embryo fibroblasts produce two types of interferon upon stimulation with Newcastle disease virus. Vet. Immunol. Immunopathol. 57, 289-303.
[104] Pene, J., Rousset, F., Briere, R, Chretien, I., Bonnefoy, J.Y., Spits, H., Yokota, T., Arai, N., Arai, K., Banchereau, J., de Vries, J. 1988. IgE production by normal human lymphocytes is induced by interleukin 4 and suppressed by interferons gamma and alpha and prostaglandin E2. Proc. Natl. Acad. Sci. U. S. A. 85,6880-6684.
[105] Braun, D., Caramalho, I., Demengeot, J. 2002. IFN-alpha/beta enhances BCR-dependent B cell responses. Int. Immunol. 14,411-419.
[106] Hunter, C.A., Gabriel, K.E., Radzanowski, T., Neyer, L.E., Remington, J.S. 1997. Type I interferons enhance production of IFN-gamma by NK cells. Immunol. Lett. 59,1-5.
[107] Nistico, P., Tecce, P., Giacomini, P., Cavallari, A., Dagnano, I., Fisher, P.B., Natali, P.G 1990. Effect of recombinant human-leukocyte, fibroblast, and immune interferons on expression of class-I and class-II major histocompatibilty complex and invariant chain in early passage human-melanoma cells. Cancer Res. 50,7422-7429.
[108] Belardelli, F. 1995. Role of interferons and other cytokines in the regulation of the immune response. APMIS. 103,161-179.
[109] Montoya, M., Schiavoni, G., Mattei, F., Gresser, I., Belardelli, F., Borrow, P., Tough, D.F. 2002. Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99, 3263-3271.
[110] Santini, S.M., Lapenta, C., Logozzi, M., Parlato, S., Spada, M., Di Pucchio, T., Belardelli, F. 2000. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp. Med. 191,1777-1788.
[111] Finkelman, F.D., Svetic, A., Gresser, I., Snapper, C., Holmes, J., Trotta, P.P., Katona, I.M., Gause, W.C. 1991. Regulation by interferon alpha of immunoglobulin isotype selection and lymphokine production in mice. J. Exp. Med. 174,1179-1188.
[112] Nakajima, H., Nakao, A., Watanabe, Y., Yoshida, S., Iwamoto, I. 1994. IFN-alpha inhibits antigen-induced eosinophil and CD4+ T cell recruitment into tissue. J. Immunol. 153,1264-1270.
[113] Taylor, J.L. and Grossberg, S.E. 1998. The effects of interferon-alpha on the production and action of other cytokines. Semin. Oncol. 25,23-29.
[114] Mitani, Y, Takaoka, A., Kim, S.H., Kato, Y, Yokachi, T., Tanaka, N., Taniguchi, T. 2001. Cross talk of the interferon-alpha/beta signaling complex with gp130 for effective interleukin-6 signaling. Genes to cells 6,631-640.
[115] Takaoka, A., Mitani, Y, Suemori, H., Sato, M., Yokochi, T., Noguchi, S., Tanaka, N., Taniguchi, T. 2000. Cross talk between interferon-gamma and -alpha/-beta signaling components in caveolar membrane domains. Science 288,2357-2360.
[116] Biron, C.A. 1998. Role of early cytokines, including alpha and beta interferons (IFN-alpha/beta), in innate and adaptive immune responses to viral infections. Seminars in immunology 10,383-390.
[117] Smith, T.J. and Wagner, R.R. 1967. Rabbit macrophage interferons. I. Conditions for biosynthesis by virus-infected and uninfected cells. J. Exp. Med. 125, 559-577.
[118] Belardelli, F., Vignaux, F., Proietti, E., Grosser, I. 1984. Injection of mice with antibody to interferon renders peritoneal macrophages permissive for vesicular stomatitis virus and encephalomyocarditis virus. Proc. Natl. Acad. Sci. U.S.A. 81,602-606.
[119] Vogel, S.N. and Fertsch, D. 1984. Endogenous interferon production by endotoxin-responsive macrophages provides an autostimulatory differentiation signal. Infect. Immun. 45,417-423.
[120] Zhang, X., Alley, E.W., Russell, S.W., Morrison, D.C. 1994. Necessity and sufficiency of beta interferon for nitric oxide production in mouse peritoneal macrophages. Infect. Immun. 62, 33-40.
[121] Gessani, S., Puddu, P., Varano, B., Borghi, P., Conti, L., Fantuzzi, L., Belardelli, F. 1994. Induction of beta interferon by human immunodeficiency virus type 1 and its gp120 protein in human monocytes-macrophages: role of beta interferon in restriction of virus replication. J. Virol. 68, 1983-1986.
[122] Meltzer, M.S., Nakamura, M., Hansen, B.D., Turpin, J.A., Kalter, D.C., Gendelman, H.E. 1990. Macrophages as susceptible targets for HIV infection, persistent viral reservoirs in tissue, and key immunoregulatory cells that control levels of virus replication and extent of disease. AIDS Res. Hum. Retroviruses. 6,967-971.
[123] Folks, T.M., Clouse, K.A., Justement, J., Rabson, A., Duh, E., Kehrl, J.H., Fauci, A.S. 1989. Tumor necrosis factor alpha induces expression of human immunodeficiency virus in a chronically infected T-cell clone. Proc. Natl. Acad. Sci. U. S. A. 86,2365-2368.
[124] Gendelman, H.E., Baca, L.M., Kubrak, C.A., Genis, P., Burrous, S., Friedman, R.M., Jacobs, D., Meltzer, M.S. 1992. Induction of IFN-alpha in peripheral blood mononuclear cells by HIV-infected monocytes. Restricted antiviral activity of the HIV-induced IFN. J. Immunol. 148,422-429.
[125] Cheng, G, Zhao, X., Yan W.Y., et al. 2007. Alpha interferon is a powerful adjuvant for a recombinant protein vaccine against foot-and-mouth disease virus in swine, and an effective stimulus of in vivo immune response. Vaccine 25, 5199-5208.
[126] Tough, D.F., Borrow, P., Sprent, J. 1996. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947-1950.
[127] Marrack, P., Kapoler, J., Mitchell, T. 1999. Type I interferons keep activated T cells alive. J Exp. Med. 189,521-529.
[128] Luft, T, Pang, K.C., Thomas, E., Hertzog, P., Hart, D.N.J., Trapani, J., Cebon, J. 1998. Type I IFNs enhance the terminal differentiation of dendritic cells. J. Immunol. 161,1947-1953.
[129] Paquette, R.L., Hsu, N.C., Kiertscher, S.M., Park, A.N., Tran, L., Roth, M.D., Glaspy, J.A. 1998. Interferon-alpha and granulocyte-macrophage colony stimulating factor differentiate peripheral blood monocytes into potent antigen presenting cells. J. Leukoc. Biol. 64, 358-367.
[130] Wang, J.Y., Lin, Q., Langston, H., Cooper, M.D. 1995. Resident bone marrow macrophages produce type 1 interferons that can selectively inhibit interleukin-7-driven growth of B lineage cells. Immunity 3,475-484.
[131] Su, D.M., Wang, J., Lin, Q, Cooper, M.D., Watanabe, T. 1997. Interferons α/β inhibit IL-7-induced proliferation of CD4- CD8- CD3- CD44+ CD25+ thymocytes, but do not inhibit that of CD4- CD8- CD3- CD44- CD25- thymocytes. Immunology 90,543-549.
[132] Demengeot, J., Vasconcellos, R., Modigliani, Y., Grandien, A., Coutinho, A. 1997. B lymphocyte sensitivity to IgM receptor ligation is independent of maturation stage and locally determined by macrophage-derived IFN-beta. Int. Immunol. 9,1677-1685.
[133] Vasconcellos, R., Braun, D., Coutinho, A., Demengeot, J. 1999. Type I IFN sets the stringency of B cell repertoire selection in the bone marrow. Int. Immunol. 11,279-288.
[134] Le Bon, A., Schiavoni, G, D Agostino, G, Gresser, I., Belardelli, F., Tough, D.F. 2001. Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14,461-470.
[1]Sen,G.C.and Lengyel,P.1992.The interferon system.A bird's eye view of its biochemistry.J.Biol.Chem.267,5017-5020.
[2]Flores,I.,Mariano,T.M.,Pestka,S.1991.Human interferon-co(omega) binds to the alpha/beta receptor.J.Biol.Chem.266,19875-19877.
[3]Pestka,S.,Langer,J.A.,Zoon,K.C.,Samuel,C.E.1987.Interferons and theirs actions.Annu.Rev.Biochem.56,727-777.
[4]Hardy,M.P.,Owczarek,C.M.,Jermiin,L.S.,Ejdeback,M.,Hertzog,P.J.2004.Characterization of the type Ⅰ interferon locus and identification of novel genes.Genomics 84,331-345.
[5]LaFleur,D.W.,Nardelli,B.,Tsareva,T.,Mather,D.,Feng,P.,Semenuk,M.,Taylor,K.,Buergin,M.,Chinchilla,D.,Roshke,V.,Chen,G.,Ruben,S.M.,Pitha,P.M.,Coleman,T.A.,Moore,P.A.2001.Interferon-kappa,a novel type Ⅰinterferon expressed in human keratinocytes.J.Biol.Chem.276,39765-39771.
[6]Oritani,K.,Medina,K.L.,Tomiyama,Y.,Ishikawa,J.,Okajima,Y.,Ogawa, M., Yokota, T., Aoyama, K., Takahashi, I., Kincade, P.W., Matsuzawa, Y. 2000. Limitin: an interferon-like cytokine that preferentially influences B lymphocyte precursors. Nat. Med. 6,659-666.
[7] Oritani, K., Kincade, P.W., Zhang, C., Tomiyama, Y., Matsuzawa, Y. 2001. Type I interferons and limitin: a comparison of structures, receptors, and functions. Cytokine & Growth Factor Rev. 12,337-348.
[8] Sheppard, P., Kindsvogel, W., Xu, W.F., et al. 2003. IL-28, IL-29 and their class II cytokine receptor IL-28R. Nature Immunol. 4,63-68.
[9] Kotenko, S.V., Galagher, G., Baurin, V.V., Lewis-Antes, A., Shen, M., Shah, N.K., Langer, J.A., Sheikh, F., Dickensheets, H., Donnelly, R.P. 2003. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat Immunol. 4,69-77
[10] Demmers, K.J., Derecka, K., Flint, A., 2001. Trophoblast interferon and pregnancy. Reproduction 121,41-49.
[11] Lefevre, F., Guillomot, M., D'Andrea, S., Battegay, S., La Bonnardiere, C. 1998. Interferon-delta: the first member of a novel type I interferon family. Biochimie 80, 779- 788.
[12] Roberts, R.M., Ealy, A.D, Alexenko, A.P., Han, C.S., Ezashi, T. 1999. Trophoblast interferons. Placenta 20,259-264.
[13] Weissmann, C. and Weker, H. 1986. The interferon genes. Prog. Nucleic. Acid Res. Mol. Biol. 33,251-300.
[14] Diaz, M.O., Pomykala, H.M., Bohlander, S.K., Maltepe, E., Malik, K., Brownstein, B., Olopade, O.I. 1994. Structure of the human type-I interferon gene cluster determined from a YAC clone contig. Genomics 22,540-552.
[15] Kelley, K. A., Kozak, C. A., Dandoy, F., Sor, F., Skup, D., Windass, J.D., DeMaeyer-Guignard, J., Pitha, P.M., DeMaeyer, E. 1983. Mapping of murine inferferon-a genes to chromosome 4. Gene 26,181-188.
[16] Kelley, K. A. and Pitha, P. M., 1985. Characterization of a mouse interferon gene locus I. Isolation of a cluster of four a-interferon genes. Nucleic Acids Res. 13, 805-823.
[17] van Pesch, V. and Michiels, T. 2003. Characterization of interferon-alpha 13, a novel constitutive murine interferon-alpha subtype. J. Biol. Chem. 278, 46321-46328.
[18] van Pesch, V., Lanaya, H., Renauld, J.C., Michiels, T. 2004. Characterization of the murine alpha interferon gene family. J. Virol. 78, 8219-8228.
[19] Yerle, M., Gellin, J., Echard, G., Lefevre, F., Gillois, M. 1986. Chromosomal localization of leukocyte interferon gene in the pig (Sus scrofa domestica L.) by in situ hybridization. Cytogenet Cell Genet. 42,129-132.
[20] Lefevre, F. and La Bonnardiere, C. 1986. Molecular cloning and sequencing of a gene encoding biologically active porcine alpha-interferon. J Interferon Res. 6, 349-360.
[21] Lefevre, F., Mege, D., Haridon, R.L., Bernard, S., Vaureix, C.D., La Bonnardiere, C. 1990. Contribution of molecular biology to the study of the porcine interferon system. Vet. Microbiol. 23,245-257.
[22] Lefevre, F., Haridon, R.L., Cuesta, F.B., La Bonnardiere, C. 1990. Production, purification and biological properties of an Escherichia coli-derived recombinant porcine alpha interferon. J. Gen. Virol. 71,1057-1063.
[23] La Bonnardiere, C., Lefevre, F., Charley, B. 1994. Interferon response in pigs: molecular and biological aspects. Vet. Immunol. Immunopathol. 43,29-36.
[24] Cheng, G., Zhao, X., Yan W.Y., et al. 2007. Alpha interferon is a powerful adjuvant for a recombinant protein vaccine against foot-and-mouth disease virus in swine, and an effective stimulus of in vivo immune response. Vaccine 25,5199-5208.
[25] Chinsangaram, J., Piccone, M.E., Grubman, M.J. 1999. Ability of foot-and-mouth disease virus to form plaques in cell culture is associated with suppression of alpha/beta interferon. J. Virol. 73,9891-9898.
[26] Chinsangaram, J., Koster, M., Grubman, M.J. 2001. Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase. J. Virol. 75, 5498-5503.
[27] Chinsangaram, J., Moraes, M.P., Koster, M., Grubman, M.J. 2003. Novel viral disease control strategy: Adenovirus expressing alpha interferon rapidly protects porcine from foot-and-mouth disease. J. Virol. 77, 1621-1625.
[28] Valarcher, J.F., Furze, J., Wyld, S., Cook, R., Conzelmann, K.K., Taylor, G. 2003. Role of alpha/beta interferons in the attenuation and immunogenicity of recombinant bovine respiratory syncytial viruses lacking NS proteins. J. Virol. 77, 8426-8439.
[29] Moraes, M.P., Chinsangaram, J., Brum, M.C., Grubman, M.J. 2003. Immediate protection of porcine from foot-and-mouth disease: a combination of adenoviruses expressing interferon alpha and a foot-and-mouth disease virus subunit vaccine. Vaccine 22,268-279.
[30] Hughes, T.K., Chin, R., Tyring, S.K., Rady, P.L. 1994. Distinction of mouse interferon-alpha subtypes by polymerase chain-reaction utilizing consensus primers and type-specific oligonucleotide probes. J. Interf. Res. 14,117-120.
[31] Fung, M.C., Sia, S.F., Leung, K.N., Mak, N.K. 2004. Detection of differential expression of mouse interferon-alpha subtypes by polymerase chain reaction using specific primers. J. Immunol. Methods 284,177-186.
[32] Corpet, F. 1988. Multiple sequence alignment with hierarchical clustering. Nucleic Acids Res. 16,10881-10890.
[33] Combet, C., Blanchet, C., Geourjon, C., Deleage, G. 2000. NPS@: network protein sequence analysis. Trends Biochem. Sci. 25,147-150.
[34] Thompson, J.D., Gibson, T.J., Plewniak, F., Jeanmougin, F., Higgins, D.G. 1997. The Clustal-X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res. 24, 4876-4882.
[35] Posada, D. and Crandall, K.A. 1998. MODELTEST: testing the model of DNA substitution. Bioinformatics 14, 817-818.
[36] Marc, R.R. and Dorothee, H. 2000. RRTree: Relative-Rate Tests between groups of sequences on a phylogenetic tree. Bioinformatics 16,296-297.
[37] Yang, Z. 2000. Phylogenetic analysis by maximun likelihood (PAML). Version 3.0. University College London, England.
[38] Pol, J.M., Broekhuysen-Davies J.M., Wagenaar F., La Bonnardiere C. 1991. The influence of porcine recombinant interferon-alpha 1 on pseudorabies virus infection of porcine nasal mucosa in vitro. J Gen. Virol. 72, 933-938.
[39] Braganca, J., Genin, P., Bandu, M.T., Darracq, N., Vignal, M., Casse, C., Doly, J., Civas, A. 1997. Synergism between multiple virus-induced factor-binding elements involved in the differential expression of interferon alpha genes. J. Biol. Chem. 272,22154-22162.
[40] Lin, R.T., Mamane, Y., Hiscott, J. 2000. Multiple regulatory domains control IRF-7 activity in response to virus infection. J. Biol. Chem. 275, 34320-34327.
[41] Juang, Y.T., Lowther, W., Kellum, M., Au, W.C., Lin, R., Hiscott, J., Pitha, P.M. 1998. Primary activation of interferon A and interferon B gene transcription by interferon regulatory factor 3. Proc. Natl. Acad. Sci. U. S. A. 95, 9837-9842.
[42] Naf, D., Hardin, S.E, Weissmann, C. 1991. Multimerization of AAGTGA and GAAAGT generates sequences that mediate virus inducibility by mimicking an interferon promoter element. Proc. Natl. Acad. Sci. U. S. A. 88,1369-1373.
[43] Morin, P., Braganca, J., Bandu, M.T., Lin, R., Hiscott, J., Doly, J., Civas, A. 2002. Preferential binding sites for interferon regulatory factors 3 and 7 involved in interferon-A gene transcription. J. Mol. Biol. 316,1009-1022.
[44] Radhakrishnan, R., Walter, L.J., Hruza, A., Reichert, P., Trotta, P.P., Nagabhushan, T.L., Walter, M.R. 1996. Zinc mediated dimer of human interferon-alpha (2b) revealed by X-ray crystallography. Structure 4, 1453-1463.
[45] Cheng G., Chen, W.Z., Li, Z.F., Yan, W.Y., Zhao, X., Xie, J., Liu, M.Q., Zhang, H., Zhong, Y. Zheng, Z.X. 2006. Characterization of the porcine alpha interferon multigene family. Gene 382,28-38.
[46] Force, A., Lynch, M., Pickett, F.B., Amores, A., Yan, Y.L., Postlethwait, J. 1999. Preservation of duplicate genes by complementary, degenerative mutations. Genetics 151,1531-1545.
[47] Hibbert, L. and Foster, G.R. 1999. Human type I interferons differ greatly in their effects on the proliferation of primary B cells. J. Interf. Cytokine Res. 19, 309-318.
[48] Santodonato, L., Ferrantini, M., Palombo, F., Aurisicchio, L., Delmastro, P., La Monica, N., Di Marco, S., Ciliberto, G., Du, M.X., Taylor, M.W., Belardelli, F. 2001. Antitumor activity of recombinant adenoviral vectors expressing murine IFN-alpha in mice injected with metaSTATic IFN-resistant tumor cells. Cancer Gene Ther. 8, 63-72.
[49] Yeow, W.S., Lawson, C.M., Beilharz, M.W. 1998. Antiviral activities of individual murine IFN-alpha subtypes in vivo: intramuscular injection of IFN expression constructs reduces cytomegalovirus replication. J. Immunol. 160, 2932-2939.
[50] Larrea, E., Alberdi, A., Castelruiz, Y, Boya, P., Civeira, M.P., Prieto, J. 2001. Expression of interferon-alpha subtypes in peripheral mononuclear cells from patients with chronic hepatitis C: a role for interferon-alpha 5. J. Viral Hepatitis 8, 103-110.
[51] Wang, A.M., Doyle, M.V., Mark, D.F. 1989. Quantitation of mRNA by the polymerase chain reaction. Proc. Natl. Acad. Sci. U. S. A. 86,9717-9721.
[52] Gilliland, G., Perrin, S., Blanchard, K., Bunn, H.F. 1990. Analysis of cytokine messenger-RNA and DNA-detection and quantitation by competitive polymerase chain-reaction. Proc. Natl. Acad. Sci. U. S. A. 87,2725-2729.
[53] Babu, J.S., Kanangat, S., Rouse, B.T. 1993. Limitations and modifications of quantitative polymerase chain reaction-application to measurement of multiple messenger-RNAs present in small amounts of sample RNA. J. Immunol. Methods 165,207-216.
[54] Reiner, S.L., Zheng, S.C., Corry, D.B., Locksley, R.M. 1993. Constructing polycompetitor cDNAs for quantitative PCR. J. Immunol. Methods 165, 37-46.
[55] Kozbor, D., Hyjek, E., Wiaderkiewicz, R., Wang, Z., Wang, M., Loh, E. 1993. Competitor messenger-RNA fragments for quantitation of cytokine specific transcripts in cell lysates. Mol. Immunol. 30,1-7.
[56] Kamstrup, S., Verthelyi, D., Klinman, D.M. 2001. Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotides. Veterinary Microbiology 78,353-362.
[57] Johansson, E., Wallgren, P., Fuxler, L., Domeika, K., Lefevre, F., Fossum, C. 2002. The DNA vaccine vector pcDNA3 induces IFN-alpha production in pigs. Vet. Immunol. Immunopathol. 87,29-40.
[58] Magnusson, M., Johansson, E., Berg, M., Eloranta, M.L., Fuxler, L., Fossum, C. 2001. The plasmid pcDNA3 differentially induces production of interferon-alpha and interleukin-6 in cultures of porcine leukocytes. Vet. Immunol. Immunopathol. 78,45-56.
[1]Pestka,S.,Langer,J.A.,Zoon,K.C.,and Samuel,C.E.1987.Interferons and their actions.Annu.Rev.Biochem.56,727-777.
[2]Maeyer,E.,and Maeyer-Guignard,J.1998.The Cytokine Handbook (Thompson,A.,ed) 3rd Ed.,pp.491-516,Academic Press,San Diego,CA.
[3]LaFleur,D.W.,Nardelli,B.,Tsareva,T.,Mather,D.,Feng,P.,Semenuk,M.,Taylor,K.,Buergin,M.,Chinchilla,D.,Roshke,V.,Chen,G.,Ruben,S.M.,Pitha,P.M.,Coleman,T.A.,Moore,P.A.2001.Interferon-kappa,a novel type Ⅰinterferon expressed in human keratinocytes.J.Biol.Chem.276,39765-39771.
[4]Krausea,C.D.and Pestka,S.2005.Evolution of the Class 2 cytokines and receptors,and discovery of new friends and relatives.Pharmacology &Therapeutics 106,299-346.
[5]Pestka,S.,Krause,C.D.,Walter,M.R.2004.Interferons,interferon-like cytokines and their receptor.Immunological Reviews 202,8-32.
[6]Cheng,G.,Zhao,X.,Chen,W.Z.,Yah,W.Y.,Liu,M.Q.,Chen,J.,Zhao,X.Z.2007.Detection of Differential Expression of Porcine IFN-α Subtypes by Reverse Transcription Polymerase Chain Reaction.Journal of interferon and cytokine research 27,579-587.
[7]Demmers,K.J.,Derecka,K.,Flint,A.2001.Trophoblast interferon and pregnancy.Reproduction 121,41-49.
[8]Roberts,R.M.,Ealy,A.D.,Alexenko,A.P.,Han,C.S.,Ezashi,T.1999.Trophoblast interferons.Placenta 20,259-264.
[9] Nardelli, B., Zaritskaya, L., Semenuk, M., Cho, Y.H., La Fleur, D.W., Shah, D., Ullrich, S., Girolomoni, G., Albanesi, C., Moore, P.A. 2002. Regulatory effect of IFN-κ, A novel type I IFN, on cytokine production by cell of the innate immune system. J. Immunol. 169,4822-4830.
[10] Lefevre F, Guillomot M, D'Andrea S, Battegay S, La Bonnardiere C. 1998. Interferon-detla: the first member of a novel type I interferon family. Biochimie 80,779-788.
[11] Oritani, K., Medina, K.L., Tomiyama, Y., Ishikawa, J., Okajima, Y., Ogawa, M., Yokota, T., Aoyama, K., Takahashi, I., Kincade, P.W., Matsuzawa, Y. 2000. Limitin: an interferon-like cytokine that preferentially influences B lymphocyte precursors. Nat. Med. 6,659-666.
[12] Oritani, K., Kincade, P.W., Zhang, C., Tomiyama, Y., Matsuzawa, Y. 2001. Type I interferons and limitin: a comparison of structures, receptors, and functions. Cytokine & Growth Factor Rev. 12,337-348.
[13] Cavalieri, R.L., Havell, E.A., Vileck, J., Pestka, S. 1977. Induction and decay of human fibroblast interferon mRNA. Proc. Natl. Acad. Sci. U. S. A. 74, 4415-4419.
[14] Raj, N.B., and Pitha, P.M. 1983. Two levels of regulation of beta-interferon gene expression in human cells. Proc. Natl. Acad. Sci. U. S. A. 80,3923-3927.
[15] Uze, G., Lutfalla, G., Gresser, I. 1990. Knockout and reconstitution of a functional human type I interferon receptor complex. Cell 60,225-234.
[16] Soh, J., Mariano, T.M., Lim, J.K., Izotova, L., Mirochnitchenko, O., Schwartz, B., Langer, J.A., Pestka, S. 1994. Expression of a functional human type I interferon receptor in hamster cells: application of functional yeast artificial chromosome (YAC) screening. J. Biol. Chem. 269,18102-18110.
[17] Domanski, P., Witte, M., Kellum, M., Rubinstein, M., Hackett, R., Pitha, P., Colamonici, O.R. 1995. Cloning and expression of a long form of the beta subunit of the interferon alpha beta receptor that is required for signaling. J. Biol. Chem. 270,21606-21611.
[18] Pestka, S. 1997. The interferon receptors. Semin. Oncol. 24, S9.
[19] Stark, G.R., Kerr, I.M., Williams, B.R., Silverman, R.H., Schreiber, R.D. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67,227-264.
[20] Schindler, C, and Darnell, J.E. 1995. Transcriptional responses to polypeptide ligands: the JAK-STAT pathway. Ann. Rev. Biochem. 64,621-651.
[21] Stark, G.R., Kerr, I.M., Williams, B.R., Silverman, R.H., Schreiber, R.D. 1998. How cells respond to interferons. Annu. Rev. Biochem. 67,227-264.
[22] Gutterman, J.U. 1994. Cytokine therapeutics: lessons from interferon alpha. Proc. Natl. Acad. Sci. U. S. A. 91,1198-1205.
[23] Schultz, J., Milpetz, F., Bork, P., Ponting, C.P. 1998. SMART, a simple modular architecture research tool: Identification of signaling domains. Proc. Natl. Acad. Sci. U. S. A. 95,5857-5864.
[24] Letunic, I., Copley, R.R., Pils, B., Pinkert, S., Schultz, J., Bork, P. 2006. SMART 5: domains in the context of genomes and networks. Nucleic Acids Research 34, D257-D260.
[25] Lefevre, R, Guillomot, M., D'Andrea, S., Battegay, S., La Bonnardiere, C. 1998. Interferon-detla: the first member of a novel type I interferon family. Biochimie 80, 779-788.
[26] Kotenko, S.V., Gallagher, G., Baurin, V.V., Lewis-Antes, A., Shen, M., Shah, N.K., Langer, J.A., Sheikh, R, Dickensheets, H., Donnelly, R.P. 2003. IFN-λs mediate antiviral protection through a distinct class II cytokine receptor complex. Nat. Immunol. 4,69-77.
[27] Quadt-Akabayov, S.R., Chill, J.H., Levy, R., Kessler, N., Anglister J. 2006. Determination of the human type I interferon receptor binding site on human interferon-a2 by cross saturation and an NMR-based model of the complex. Protein Science 15,2656-2668.
[28] Chill, J.H., Nivasch, R., Levy,R., Albeck, S., Schreiber, G., Anglister, J. 2002. The human interferon receptor: NMR-Based modeling, mapping of the IFN-R2 binding site, and observed Ligand-Induced tightening. Biochemistry 41,3575-3585.
[29] Chill, J.H., Quadt, S.R., Levy, R., Schreiber, G., Anglister, J. 2003. The Human Type I Interferon Receptor: NMR Structure Reveals the Molecular Basis of Ligand Binding. Structure 11, 791-802.
[30] Torrence, P.F. et al. 1985. How interferon works. In Biological response modifiers. pp. 77-119, Orlando: Academic Press.
[31] Sandberg, K., Eloranta, M.L., Campbell, I.L. 1994. Expression of alpha/beta interferons and their relationship to IFN-alpha/beta-induced genes in lymphocytic choriomeningitis. J Virol. 68, 7358-7366.
[32] McDowell, M.A., Lucas, D.M., Nicolet, C.M., Paulnock, D.M. 1995. Differential utilization of IFN-responsive element in two maturationally distinct Macrophage cell lines.J.lmmunol.155,4933-4941.
[33]Le Bon,A.,Tough,D.F.2002.Links between innate and adaptive immunity via type Ⅰ interferon.Current Opinion in Immunology.14,432-436.
[34]Alexopoulou,L.,Holt,A.C.,Medzhitov,R.,Flavell,R.A.2001.Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3.Nature 413,732-738.
[35]Milone,M.C.and Fitzgerald-Bocarsly,P.1998.The mannose receptor mediates induction of interferon-alpha in peripheral blood dendritic cells by enveloped RNA and DNA viruses.J.Immunol.161,2391-2399.
[1] Belsham, G.J. 1993. Distinctive features of foot-and-disease virus, a member of the picornavirus family-aspects of virus protein-synthesis, protein processing and structure. Prog. Biophys. Mol. Biol. 60,241-260.
[2] Pereira, H.G. 1981. Foot-and-mouth disease. In: Gibbs EPJ, editor. Virus Diseases of Food Animals. pp. 333-363, London, Academic Press Inc.
[3] Barteling, S.J. and Vreeswijk, J. 1991. Developments in foot-and-mouth-disease vaccines. Vaccine 9, 75-88.
[4] Baxt, B., Morgan, D.O., Roberton, B.H., Timpone, C.A. 1984. Epitopes on foot-and-mouth disease virus outer capsid protein VP1 involved in neutralization and cell attachment. J Virol. 51,298-305.
[5] Collen, T., Dimarchi, R., Doel, T.R. 1991. A T-cell epitope in VP1 of foot-and-mouth-disease virus is immunodominant for vaccinated cattle. J Immunol. 146, 749-755.
[6] Strohmaier, K., Franze, R., Adam, K.H. 1982. Location and characterization of the antigenic portion of the FMDV immunizing protein. J Gen. Virol. 59, 295-306.
[7] Li, G.J., Chen, W.Z., Yan, W.Y., Zhao, K., Liu, M.Q., Zhang, J., Fei, L., Xu, Q.X., Sheng, Z.T., Lu, Y.G., Zheng, Z.X. 2004. Comparison of immune responses against foot-and-mouth disease virus induced by fusion proteins using the swine IgG heavy chain constant region or beta-galactosidase as a carrier of immunogenic epitopes. Virology 328,274-281.
[8] Le Bon, A., Schiavoni, G., D'Agostino, G., Gresser, I., Belardelli, F., Tough, D.F. 2001. Type I interferons potently enhance humoral immunity and can promote isotype switching by stimulating dendritic cells in vivo. Immunity 14, 461-470.
[9] Braun, D., Caramalho, I., Demengeot, J. 2002. IFN-alpha/beta enhances BCR-dependent B cell responses. Int. Immunol. 14,411-419.
[10] Hunter, C.A., Gabriel, K.E., Radzanowski, T., Neyer, L.E., Remington, J.S. 1997. Type I interferons enhance production of IFN-gamma by NK cells. Immunol. Lett. 59,1-5.
[11] Tough, D.F., Borrow, P., Sprent, J. 1996. Induction of bystander T cell proliferation by viruses and type I interferon in vivo. Science 272, 1947-1950.
[12] Marrack, P., Kapoler, J., Mitchell, T. 1999. Type I interferons keep activated T cells alive. J Exp. Med. 189,521-529.
[13] Nistico, P., Tecce, P., Giacomini, P., Cavallari, A., Dagnano, I., Fisher, P.B., Natali, P.G. 1990. Effect of recombinant human-leukocyte, fibroblast, and immune interferons on expression of class-I and class-II major histocompatibilty complex and invariant chain in early passage human-melanoma cells. Cancer Res. 50,7422-7429.
[14] Luft, T., Pang, K.C., Thomas, E., Hertzog, P., Hart, D.N.J., Trapani, J., Cebon, J. 1998. Type I IFNs enhance the terminal differentiation of dendritic cells. J Immunol. 161,1947-1953.
[15] Montoya, M., Schiavoni, G., Mattei, F., Gresser, I., Belardelli, F., Borrow, P., Tough, D.F. 2002. Type I interferons produced by dendritic cells promote their phenotypic and functional activation. Blood 99,3263-3271.
[16] Santini, S.M., Lapenta, C, Logozzi, M., Parlato, S., Spada, M., Di Pucchio, T., Belardelli, F. 2000. Type I interferon as a powerful adjuvant for monocyte-derived dendritic cell development and activity in vitro and in Hu-PBL-SCID mice. J Exp. Med. 191,1777-1788.
[17] Taylor, J.L. and Grossberg, S.E. 1998. The effects of interferon-alpha on the production and action of other cytokines. Semin. Oncol. 25,23-29.
[18] Mitani, Y, Takaoka, A., Kim, S.H, Kato, Y., Yokachi, T., Tanaka, N., Taniguchi, T. 2001. Cross talk of the interferon-alpha/beta signaling complex with gp130 for effective interleukin-6 signaling. Genes to cells 6,631-640.
[19] Takaoka, A., Mitani, Y., Suemori, H., Sato, M., Yokochi, T., Noguchi, S., Tanaka, N., Taniguchi, T. 2000. Cross talk between interferon-gamma and -alpha/-beta signaling components in caveolar membrane domains. Science 288,2357-2360.
[20] Biron, C.A. 1998. Role of early cytokines, including alpha and beta interferons (IFN-alpha/beta), in innate and adaptive immune responses to viral infections. Seminars in immunology 10,383-390.
[21] Proietti, E., Bracci, L., Puzelli, S., Di Pucchio, T., Sestili, P., De Vincenzi, E., Venditti, M., Capone, I., Seif, I., De Maeyer, E., Tough, D., Donatelli, I., Belardelli, F. 2002. Type I IFN as a natural adjuvant for a protective immune response: Lessons from the influenza vaccine model. J Immunol. 169, 375-383.
[22] Bracci, L., Canini, I., Puzelli, S., Sestili, P., Venditti, M., Spada, M., Donatelli, I., Belardelli, F., Proietti, E. 2005. Type I IFN is a powerful mucosal adjuvant for a selective intranasal vaccination against influenza virus in mice and affects antigen capture at mucosal level. Vaccine 23,2994-3004.
[23] de Avila Botton, S., Brum, M.C.S., Bautista, E., Koster, M., Weiblen, R., Golde, W.T., Grubman, M.J. 2006. Immunopotentiation of a foot-and-mouth disease virus subunit vaccine by interferon alpha. Vaccine 24, 3446-3456.
[24] Cheng, G., Chen, W.Z., Li, Z.F., Yan, W.Y., Zhao, X., Xie, J., Liu, M.Q., Zhang, H., Zhong, Y., Zheng, Z.X. 2006. Characterization of the porcine alpha interferon multigene family. Gene 382,28-38.
[25] Kirby, C. and Gregoriadis, G. 1984. Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes. Biotechnology 11, 979-984.
[26] Golding, S.M., Hedger, R.S., Talbot, P. 1976. Radial immuno-diffusion and serum-neutralisation techniques for the assay of antibodies to swine vesicular disease. Res. Vet. Sci. 20,142-147.
[27] Kang, Y.M., Jin, H., Zheng, G.X., Xie, Q.F., Yin, J.M., Yu, Y., Xiao, C., Zhang, X.Y., Chen, A.S., Wang, B. 2005. The adjuvant effect of levamisole on killed viral vaccines. Vaccine 23, 5543-5550.
[28] Maghni, K., Nicolescu, O.M., Martin, J.G. 1999. Suitability of cell metabolic colorimetric assays for assessment of CD4~+ T cell proliferation: comparison to 5-bromo-2-deoxyuridine (BrdU) ELISA. Journal of Immunological Methods 223,185-194.
[29] Barnett, P.V., Cox, S.J., Aggarwal, N., Gerber, H., McCullough, K.C. 2002. Further studies on the early protective responses in pigs following immunisation with high potency foot-and-mouth disease vaccine. Vaccine 20, 3197-3208.
[30] Sun, T., Lu, P., Wang, X. 2004. Localization of infection-related epitopes on the non-structural protein 3ABC of foot-and-mouth disease virus and the application of tandem epitopes. J Virol. Methods 119, 79-86.
[31] Isaacs, A., and Lindenmann, J. 1957. Virus interference: the interferon. Proc. R. Soc. Med. 147,258-267.
[32] Dalpke, A., Zimmermann, S., Heeg, K. 2002. Immunopharmacology of CpG DNA. Biol. Chem. 383, 1491-1500.
[33] Cox, J.C. and Coulter, A.R. 1997. Adjuvants-a classification and review of their modes of action. Vaccine 15,248-256.
[34] Falcone, M. and Sarvetnick, N. 1999. Cytokines that regulate autoimmune responses. Current Opinion in Immunology 11,670-676.
[35] King, C, Davies, J., Mueller, R., Lee, M.S., Krahl, T., Yeung, B., O'Connor, E., Sarvetnick, N. 1998. TGF-betal alters APC preference, polarizing islet antigen responses toward a Th2 phenotype. Immunity 8,601-613.
[36] Mueller, R., Bradley, L.M., Krahl, T., Sarvetnick, N. 1997. Mechanism underlying counterregulation of autoimmune diabetes by IL-4. Immunity 7, 411-418.
[37] Morgan, H, Bjorn, F.L., Michael, S.K., Daniel, S.C., Mark, M.D. 2006. T cells use two directionally distinct pathways for cytokine secretion. Nature Immunology 7,247-255.
[38] Lucey, D.R., Clerici, M., Shearer, G.M. 1996. Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic, and inflammatory diseases. Clinical Microbiology Reviews 9,532.
[39] So, E.Y., Park, H.H., Lee, C.E. 2000. IFN-gamma and IFN-alpha posttranscriptionally down-regulate the IL-4-induced IL-4 receptor gene expression. The Journal of Immunology 165, 5472-5479.
[40] Chinsangaram, J., Koster, M., Grubman, M.J. 2001. Inhibition of L-deleted foot-and-mouth disease virus replication by alpha/beta interferon involves double-stranded RNA-dependent protein kinase. J Virol. 75, 5498-5503.
[41] de los Santos, T., Botton, S.D., Weiblen, R., Grubman, M.J. 2006. The leader proteinase of foot-and-mouth disease virus inhibits the induction of beta interferon mRNA and blocks the host innate immune response. J Virol. 80, 1906-1914.