共表达新城疫病毒融合蛋白基因和H9亚型禽流感病毒血凝素基因的重组鸡痘病毒及其免疫效力
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摘要
新城疫是由副粘病毒科的新城疫病毒(Newcastle diseae virus，NDV)引起的一种烈性家禽传染病，它对我国养禽业的危害最为严重。低致病性H9亚型禽流感病毒(Avian Influenza virus，AIV)是目前影响我国养禽业的主要AIV亚型，它对我国养禽业也已造成了严重的经济损失。当前我国对ND和H9亚型AI的控制主要应用常规疫苗的免疫接种。但是作为我国目前控制ND和H9亚型AI流行的重要手段，常规疫苗的免疫接种会干扰现有技术条件下的免疫监测和流行病学调查。而且油乳剂灭活疫苗使用后会引起严重应激，并且生产成本偏高等。为了研制一种可以克服上述缺点的新型载体联合疫苗，本研究用鸡痘病毒(Fowlpox viros，FPV)作为表达载体，构建了能够同时表达NDV融合蛋白(Fusion protein，F)基因和H9亚型AIV血凝素(Hemagglutinin，HA)基因的重组鸡痘病毒，并对其免疫效力进行了评估。
1．共表达NDV F基因和H9亚型AIV HA基因的重组鸡痘病毒的构建及其生物学特性鉴定
以酚-氯仿提纯NDV F48E8株的基因组RNA作为反转录聚合酶链反应(RT-PCR)模板，扩增出长度约为1.7Kb的NDV F基因片段，将其克隆入pGEM-Teasy载体，构建重组质粒pGEM-TF并进行测序确证；以质粒pUCHA为模板，用PCR扩增出约为1.7Kb的H9亚型AIV HA基因片段，将其克隆入pGEM-T easy载体，构建重组质粒pGEM-THA并进行测序确证。分别从pGEM-TF和pGEM-THA切下F基因和HA基因，通过一系列分子生物学操作步骤插入到质粒pFPV7S中的FPV基因组复制非必需片段，并使分别调控F基因和HA基因转录的鸡痘病毒启动子P_(E／L)和合成启动子P_S以反向方式连接，重组质粒命名为p7SHF。最后将P11-LacZ报告基因表达盒插入到质粒p7SHF中，获得转移载体pFPVHF，用以转
扬州大学博士学位论文
染经预先感染FPV 282E4疫苗株的鸡胚成纤维细胞(CEF).通过在含有X.Gal的
营养琼脂上挑选蓝色病毒蚀斑，经过多次蓝斑筛选和克隆纯化后，获得稳定生长
的重组鸡痘病毒(rFPv一F一HA)。PCR和Southem一blot检测证实了F基因和HA基
因已成功插入到FPV的基因组:间接免疫荧光试验结果表明重组病毒能够同时正
确表达HA和F蛋白。
比较rFPv一F一HA和wt一FPv在CEF上的繁殖滴度，结果发现两者在CEF中的繁
殖滴度无显性著差异，提示载体病毒的复制能力并未因外源基因的插入而下降。
将rFPV一F一HA在CEF上连续传代培养20代次后，蓝色空斑试验和PCR检测结果表
明插入的F基因和HA基因均能够在病毒的传代过程中稳定遗传;间接免疫荧光试
验证实第20代次的重组鸡痘病毒仍然能够正确表达F和HA蛋白，进一步表明了
rFPv一F一HA具有良好的遗传稳定性。
2.NOV「蛋白抗体的间接ELISA检测方法的建立及评估
用经过充分灭活的NDV F48E8株作为包被抗原，建立了检测由FPV载体介
导表达的NDVF蛋白的抗体的间接ELJSA方法，并用动物试验进行了初步评估。
以方阵滴定法确定抗原的最佳包被浓度为355n留孔，待检血清最佳稀释度为1:40。
通过交叉试验、阻断试验和重复性试验证实所建立的间接ELisA方法具有高度的
特异性和良好的可重复性。用该间接EUSA方法测定了20份阳性血清样品的P加
值，并通过对该20份阳性血清的P/N值与ELisA抗体效价(ELISA titer， ET)的
自然对数值(InET)的线性回归分析，获得了回归方程1 nET=0 .201 XP/N+4 .632，
通过测定待检血清在l:40稀释度的P/N值，用方程直接求出血清的ELISA抗体滴
度，可以实现定量检测。应用该间接ELISA方法对表达NDVF基因的重组鸡痘病
毒免疫鸡群进行了血清抗体检测，结果表明，血清的间接ELISA抗体效价与中和
试验所测定相应血清的中和抗体效价高度相关(P<0 .01)。攻毒保护试验结果显示，
间接ELISA抗体效价和机体保护力之间表现一定程度的相关性。该方法的建立为
后续试验评估表达NDVF基因的重组鸡痘病毒免疫鸡群的免疫效果提供了一种可
靠的血清学方法。
3.共表达NDVF基因和H9亚型AIVHA基因的重组鸡痘病毒的免疫效
力试验
3.1试验鸡接种rFPv一F一HA后抵抗H9亚型Alv感染的免疫保护作用
7日龄SPF雏鸡随机分为4组，分别于颈部皮下接种rFPv一F一HA(104PFU/羽)、
韦栋平:共表达NDVF基因和H9亚型AlvHA基因的重组鸡痘病毒及其免疫效力iii
rFPv一队(lo4PFu/羽)、wt一FPv(一o4PFu/羽)和Hg亚型Al油乳剂灭活疫苗(0.ZmL/
羽)。免疫后7~21天，除wt一FPv外，各种疫苗均可诱生针对H9亚型Alv的特异
性HI抗体。其中以油乳剂灭活疫苗诱生的HI抗体效价最高，而rFPv一F一HA诱生
的Hl抗体效价与单表达队基因的rFPV一队诱生的HI抗体效价差异不显著。免疫
后21天，各组试验鸡用剂量为107ELDS丫羽的Hg亚型川vF株滴鼻攻毒，并于攻
毒后5天采集试验鸡的口腔棉拭子，按照常规方法处理后，接种10日龄SPF鸡胚
作病毒分离试验。结果显示各组试验鸡的口腔排毒率为:wt一FPV免疫组(100%)、
rFPV一F一HA免疫组(16.7%)、rFPV一队免疫组(16.7%)和油乳剂灭活疫苗免疫组
(16.7%)。
用含有残余抗NDV和H9亚型AIV母源抗体的26日龄商品蛋鸡进行免疫效力
试验，结果发现，尽管由于母源抗体的干扰，rFPV一F一HA及rFPV一HA在商品蛋鸡体
内诱生的HI抗体效价远低于?
Both Newcastle disease (ND) and H9 subtype avian influenza (AI) have been serious disease problems and caused considerable economic losses in poultry industry in China. So far, vaccination with conventional vaccines including the attenuated live vaccines and inactivated vaccines in oil emulsion to protect birds against ND and H9 subtype AI has been a routine procedure in China. However, the use of these vaccines is restricted because of the disadvantages they inherit including their interference of routine serological surveillance, higher cost and side effect of greater streos in birds post-vaccination. Here, we described the construction of recombinant fowlpox virus co-expressing the fusion protein (F) gene of Newcastle disease virus (NDV) and the HA gene of H9 subtype avian influenza virus (AIV) and the evaluation of its protective efficacy against either NDV or AIV challenge in chickens for the development of better vaccine.
1. Construction of recombinant fowlpox virus co-expressing the F gene of NDV and the HA gene of H9 subtype AIV and its biological properties
The genomic RNA of NDV strain F48E8 was prepared by phenol-chloroform extraction and used as template for RT-PCR to obtain the fusion protein (F) gene, which was cloned into pGEM-T easy vector to form pGEM-TF and its sequence was determined. The hemagglutinin (HA) gene of H9 subtype ATV in pUCHA was modified by using PCR. Its amplified product was then inserted into pGEM-T easy vector and the resulting plasmid pGEM-THA was determined by sequencing. In order to construct recombinant plasmid p7SHF, the F gene in pGEM-TF and the HA gene in pGEM-THA were excised, respectively, and inserted into the randomly selected
nonessential region of the fowlpox virus (FPV) under the transcriptional control of fowlpox virus promoter Pe/L. and the synthetic promoter Ps, respectively, which were ligated in opposite direction. The P11-LacZ reporter gene from pppG18 was cloned into p7SHF resulting in recombinant transfer vector pFPVHF. Pre-infected with Chinese vaccine strain 282E4 of FPV (wt-FPV), chicken embryo fibroblast (CEF) monolayers was transfected with pFPVHF to generate recombinant fowlpox virus co-expressing F and HA, designated rFPV-F-HA. By selection of blue plaques on the CEF overlaid with agar containing X-Gal, rFPV-F-HA was screened and subjected to further rounds of plaque purification until a pure population was achieved. PCR and Southern-blot assay indicated that the F and HA gene had been inserted into the genomic DNA of FPV. Subsequently, F and HA expressed in CEF infected with rFPV-F-HA were confirmed by indirect immunofluorescence assay (IFA).
Comparison of the viral titer between rFPV-F-HA and wt-FPV grown in CEF demonstrated that the ability of rFPV-F-HA to replicate in CEF was not impaired for insertion of the target DNA fragments. The rFPV-F-HA was further detected by blue plaque assay and PCR after it was passaged for 20 times on CEF monolayers. These results showed that the inserted F gene and HA gene were stably integrated. Expression of F and HA in rFPV- F-HA confirmed by IFA suggested that it be genetically stable. 2. Detection of antibody in chickens to Newcastle disease virus fusion protein by indirect ELISA
An indirect ELISA for detecting antibody in chickens induced by the fusion protein of NDV expressed by recombinant fowlpox viruses (rFPVs) was developed with great sensitivity, high specificity and strong reproducibility, and subsequently evaluated with sera from SPF chickens vaccinated with or without rFPVs. The optimum coating concentration of NDV antigen was determined by checkerboard titration using pre-immune chicken antiserum to recombinant fowlpox virus expressing the F gene of NDV and amounted to 355ng of NDV antigen per well. The serum sample for detection was diluted to 1:40. A near-linear relationship existed between positive /negative ratio(P/N) of anti-sera at a single working dilution (1:40) and the In of the corresponding observed serum ELISA titers (ET) as determined by a standard serial-dilution method. Regres
1．共表达NDV F基因和H9亚型AIV HA基因的重组鸡痘病毒的构建及其生物学特性鉴定
以酚-氯仿提纯NDV F48E8株的基因组RNA作为反转录聚合酶链反应(RT-PCR)模板，扩增出长度约为1.7Kb的NDV F基因片段，将其克隆入pGEM-Teasy载体，构建重组质粒pGEM-TF并进行测序确证；以质粒pUCHA为模板，用PCR扩增出约为1.7Kb的H9亚型AIV HA基因片段，将其克隆入pGEM-T easy载体，构建重组质粒pGEM-THA并进行测序确证。分别从pGEM-TF和pGEM-THA切下F基因和HA基因，通过一系列分子生物学操作步骤插入到质粒pFPV7S中的FPV基因组复制非必需片段，并使分别调控F基因和HA基因转录的鸡痘病毒启动子P_(E／L)和合成启动子P_S以反向方式连接，重组质粒命名为p7SHF。最后将P11-LacZ报告基因表达盒插入到质粒p7SHF中，获得转移载体pFPVHF，用以转
扬州大学博士学位论文
染经预先感染FPV 282E4疫苗株的鸡胚成纤维细胞(CEF).通过在含有X.Gal的
营养琼脂上挑选蓝色病毒蚀斑，经过多次蓝斑筛选和克隆纯化后，获得稳定生长
的重组鸡痘病毒(rFPv一F一HA)。PCR和Southem一blot检测证实了F基因和HA基
因已成功插入到FPV的基因组:间接免疫荧光试验结果表明重组病毒能够同时正
确表达HA和F蛋白。
比较rFPv一F一HA和wt一FPv在CEF上的繁殖滴度，结果发现两者在CEF中的繁
殖滴度无显性著差异，提示载体病毒的复制能力并未因外源基因的插入而下降。
将rFPV一F一HA在CEF上连续传代培养20代次后，蓝色空斑试验和PCR检测结果表
明插入的F基因和HA基因均能够在病毒的传代过程中稳定遗传;间接免疫荧光试
验证实第20代次的重组鸡痘病毒仍然能够正确表达F和HA蛋白，进一步表明了
rFPv一F一HA具有良好的遗传稳定性。
2.NOV「蛋白抗体的间接ELISA检测方法的建立及评估
用经过充分灭活的NDV F48E8株作为包被抗原，建立了检测由FPV载体介
导表达的NDVF蛋白的抗体的间接ELJSA方法，并用动物试验进行了初步评估。
以方阵滴定法确定抗原的最佳包被浓度为355n留孔，待检血清最佳稀释度为1:40。
通过交叉试验、阻断试验和重复性试验证实所建立的间接ELisA方法具有高度的
特异性和良好的可重复性。用该间接EUSA方法测定了20份阳性血清样品的P加
值，并通过对该20份阳性血清的P/N值与ELisA抗体效价(ELISA titer， ET)的
自然对数值(InET)的线性回归分析，获得了回归方程1 nET=0 .201 XP/N+4 .632，
通过测定待检血清在l:40稀释度的P/N值，用方程直接求出血清的ELISA抗体滴
度，可以实现定量检测。应用该间接ELISA方法对表达NDVF基因的重组鸡痘病
毒免疫鸡群进行了血清抗体检测，结果表明，血清的间接ELISA抗体效价与中和
试验所测定相应血清的中和抗体效价高度相关(P<0 .01)。攻毒保护试验结果显示，
间接ELISA抗体效价和机体保护力之间表现一定程度的相关性。该方法的建立为
后续试验评估表达NDVF基因的重组鸡痘病毒免疫鸡群的免疫效果提供了一种可
靠的血清学方法。
3.共表达NDVF基因和H9亚型AIVHA基因的重组鸡痘病毒的免疫效
力试验
3.1试验鸡接种rFPv一F一HA后抵抗H9亚型Alv感染的免疫保护作用
7日龄SPF雏鸡随机分为4组，分别于颈部皮下接种rFPv一F一HA(104PFU/羽)、
韦栋平:共表达NDVF基因和H9亚型AlvHA基因的重组鸡痘病毒及其免疫效力iii
rFPv一队(lo4PFu/羽)、wt一FPv(一o4PFu/羽)和Hg亚型Al油乳剂灭活疫苗(0.ZmL/
羽)。免疫后7~21天，除wt一FPv外，各种疫苗均可诱生针对H9亚型Alv的特异
性HI抗体。其中以油乳剂灭活疫苗诱生的HI抗体效价最高，而rFPv一F一HA诱生
的Hl抗体效价与单表达队基因的rFPV一队诱生的HI抗体效价差异不显著。免疫
后21天，各组试验鸡用剂量为107ELDS丫羽的Hg亚型川vF株滴鼻攻毒，并于攻
毒后5天采集试验鸡的口腔棉拭子，按照常规方法处理后，接种10日龄SPF鸡胚
作病毒分离试验。结果显示各组试验鸡的口腔排毒率为:wt一FPV免疫组(100%)、
rFPV一F一HA免疫组(16.7%)、rFPV一队免疫组(16.7%)和油乳剂灭活疫苗免疫组
(16.7%)。
用含有残余抗NDV和H9亚型AIV母源抗体的26日龄商品蛋鸡进行免疫效力
试验，结果发现，尽管由于母源抗体的干扰，rFPV一F一HA及rFPV一HA在商品蛋鸡体
内诱生的HI抗体效价远低于?
Both Newcastle disease (ND) and H9 subtype avian influenza (AI) have been serious disease problems and caused considerable economic losses in poultry industry in China. So far, vaccination with conventional vaccines including the attenuated live vaccines and inactivated vaccines in oil emulsion to protect birds against ND and H9 subtype AI has been a routine procedure in China. However, the use of these vaccines is restricted because of the disadvantages they inherit including their interference of routine serological surveillance, higher cost and side effect of greater streos in birds post-vaccination. Here, we described the construction of recombinant fowlpox virus co-expressing the fusion protein (F) gene of Newcastle disease virus (NDV) and the HA gene of H9 subtype avian influenza virus (AIV) and the evaluation of its protective efficacy against either NDV or AIV challenge in chickens for the development of better vaccine.
1. Construction of recombinant fowlpox virus co-expressing the F gene of NDV and the HA gene of H9 subtype AIV and its biological properties
The genomic RNA of NDV strain F48E8 was prepared by phenol-chloroform extraction and used as template for RT-PCR to obtain the fusion protein (F) gene, which was cloned into pGEM-T easy vector to form pGEM-TF and its sequence was determined. The hemagglutinin (HA) gene of H9 subtype ATV in pUCHA was modified by using PCR. Its amplified product was then inserted into pGEM-T easy vector and the resulting plasmid pGEM-THA was determined by sequencing. In order to construct recombinant plasmid p7SHF, the F gene in pGEM-TF and the HA gene in pGEM-THA were excised, respectively, and inserted into the randomly selected
nonessential region of the fowlpox virus (FPV) under the transcriptional control of fowlpox virus promoter Pe/L. and the synthetic promoter Ps, respectively, which were ligated in opposite direction. The P11-LacZ reporter gene from pppG18 was cloned into p7SHF resulting in recombinant transfer vector pFPVHF. Pre-infected with Chinese vaccine strain 282E4 of FPV (wt-FPV), chicken embryo fibroblast (CEF) monolayers was transfected with pFPVHF to generate recombinant fowlpox virus co-expressing F and HA, designated rFPV-F-HA. By selection of blue plaques on the CEF overlaid with agar containing X-Gal, rFPV-F-HA was screened and subjected to further rounds of plaque purification until a pure population was achieved. PCR and Southern-blot assay indicated that the F and HA gene had been inserted into the genomic DNA of FPV. Subsequently, F and HA expressed in CEF infected with rFPV-F-HA were confirmed by indirect immunofluorescence assay (IFA).
Comparison of the viral titer between rFPV-F-HA and wt-FPV grown in CEF demonstrated that the ability of rFPV-F-HA to replicate in CEF was not impaired for insertion of the target DNA fragments. The rFPV-F-HA was further detected by blue plaque assay and PCR after it was passaged for 20 times on CEF monolayers. These results showed that the inserted F gene and HA gene were stably integrated. Expression of F and HA in rFPV- F-HA confirmed by IFA suggested that it be genetically stable. 2. Detection of antibody in chickens to Newcastle disease virus fusion protein by indirect ELISA
An indirect ELISA for detecting antibody in chickens induced by the fusion protein of NDV expressed by recombinant fowlpox viruses (rFPVs) was developed with great sensitivity, high specificity and strong reproducibility, and subsequently evaluated with sera from SPF chickens vaccinated with or without rFPVs. The optimum coating concentration of NDV antigen was determined by checkerboard titration using pre-immune chicken antiserum to recombinant fowlpox virus expressing the F gene of NDV and amounted to 355ng of NDV antigen per well. The serum sample for detection was diluted to 1:40. A near-linear relationship existed between positive /negative ratio(P/N) of anti-sera at a single working dilution (1:40) and the In of the corresponding observed serum ELISA titers (ET) as determined by a standard serial-dilution method. Regres
引文
[1] Pastoret P P, Vanderplasschen A. Poxvirues as vaccine vector. Comp Immunol Micro, 2003,26:333-354.
[2] Goebel S J, Johnson G P, Perkus M E, et al. The complete DNA sequence of vaccina virus. Virology, 1990,179:247-266,517-563.
[3] Boyle D B, Coupar E H. Construct of recombinant fowlpox viruses as vectors for poultry vaccines. Virus Res, 1988,10:343-356.
[4] Taylor J, Weinberg R, Languet B, et al. Recombinant fowlpox virus inducing protective immunity in non-avian species. Vaccine, 1988,6:497-503.
[5] Taylor J, Weinberg R, Kawaoka Y, et al. Protective immunity against avian influenza induced by a fowlpox virus recombinant. Vaccine, 1988,6:504-508.
[6] Afonso C L, Tulman E R, Lu Z, et al. The genome of fowlpox virus. J Virol, 2000,74:3815-3831.
[7] Laidlaw S M, Skinner M A. Comparison of the genome sequence of FP9, an attenuated, tissue culture-adapted European strain of Fowlpox virus, with those of virulent American and European viruses. J Gen Virol, 2004,85(2):305-322.
[8] 殷震，刘景华主编．动物病毒学．第二版．北京：科学出版社，1997．939-987．
[9] Buller R M, Palumbo G L. Poxvirus pathogenesis. Microbiological review, 1991,55(1):80-122.
[10] 徐耀先，周晓峰，刘立德主编．分子病毒学．第一版．武汉：湖北科学技术出版社，2000．253-264．
[11] Boulanger D, Smith T, Skinner M A. Morphogenesis and release of fowlpox virus. J Gen Virol, 2000, 81:675-687.
[12] 卡尔尼克B W主编，高福等译．禽病学．第十版．北京：北京农业出版社，2000．653-659．
[13] Baxby D, Paoletti E. Potential use of non-replicating vector as recombinant vaccines. Vaccine, 1992,10(1):8-9.
[14] Fatunmbi O F, Reed, R M. Evaluation of a commercial modified live virus fowl pox vaccine for the control of 'variant' fowl poxvirus infections, Avian Dis,1996, 40: 582-587.
[15] Tadese T, Reed W M. Detection of specific reticuloendotheliosis virus sequence and protein from REV-integrated fowlpox virus swains. J Virol Methods, 2003,110(1):99-104.
[16] Singh P, Schnitzlein W M, Tripathy D N. Reticuloendotheliosis Virus Sequences within the Genomes of Field Strains of Fowlpox Virus Display Variability. J Virol, 2003,77(10):5855-5862.
[17] Gubser C, Hue S, Kellam P, et al. Poxvirus genomes: a phylogenetic analysis. J Gen Virol, 2004, 85(1):105-117.
[18] Coupar, B E H, Teo T, Boyle D B. Restriction endonuclease mapping of the fowlpox virus genome. Virology, 1990,179:159-167.
[19] Mockett B, Binns M M, Boursnell M E G., et al. Comparison of the locations of homologgus fowlpox and vaccinia virus genes reveals major genome reorganization. J Gen Virol, 1992, 73: 2661-2668.
[20] Campbell J I A, Binns M M, Tomley F M, et al. Tandem repeated sequences within the terminal region of the fowlpox virus genome. J Gen Virol, 1989,210:771-784.
[21] Coupar B E H, Teo T, Boyle D B. Restriction endonuclease mapping of the fowlpox virus genome. Virology, 1990,179:159-167.
[22] Goebel S J, Johnson G P M, Perkus E, et al. The complete DNA sequence of vaccinia virus. Virology, 1990, 179:247-266.
[23] Massung R F, Liu L I, Qi J, et al. Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975. Virology, 1994,201:215-240.
[24] Senkevich T G, Koonin E V, Bugert J J, et al. The genome of Molluscum contagiosum virus: analysis and comparison with other poxviruses. Virology, 1997,233:19-42.
[25] Massung R F, Esposito J J, Liu L I, et al. Potential virulence determinants in terminal regions of variola smallpox virus genome. Nature, 1993,366:748-751.
[26] Senkevich T G, Bugert J J, Sisler J R, et al. Genome sequence of a human tumorigenic poxvirus: prediction of specific host response-evasion genes. Science, 1996,273:813-816.
[27] 金宁一，殷震．痘苗病毒载体研究进展．生物化学与生物物理进展，1996，23(4)：301-304．
[28] 顾万钧，金宁一．鸡痘病毒载体研究进展．吉林农业大学学报，1995，17(4)：89-95．
[29] 王志亮，刘秀梵．禽痘病毒分子生物学．中国动物检疫，1996，13(4)：31-33．
[30] Davison A J, Moss B. Structure of vaccinia virus early promotor. J Virol, 1989. 210:749-769.
[31] Kumar S, Boyle D B. Mapping of a major early/late gene of fowlpox virus. Virus Res,1990,15:175-185.
[32] Kumar S, Boyle D B. A poxvirus bidirectional promoter element with early/late and late functions. Virology, 1990,179:151-158.
[33] Zantinge J L, Krell P J, Derbyshire J B. Partial transcriptional mapping of the fowlpox virus genome and analysis of the EcoRI L fragment. J Gen Virol, 1996,77:603-614.
[34] Golini F, Kates J R. Transcriptional and translational analysis of a strongly
expressed early region of the vaccinia virus. J Virol, 1984,49(2):459-470.
[35] Ahn B, Moss B. Capped poly(A) leader of variable lengths at the ends of vaccinia virus late mRNA. J Virol, 1989,63(1)226-232.
[36] Boulanger D, Green P, Jones B, et al. Identification and characterization of three immunodominant structure proteins of fowlpox virus. J Virol, 2002,76(19):9844-9855.
[37] 余传霖，熊思东主编．分子免疫学．第一版．上海：复旦大学出版社／上海医科大学出版社，2001．815-825．
[38] Bradshaw R A, Blundell T L, Lapatto R, et al. Nerve growth factor revisited. Trends Biochem Sci,1993,18:48-52.
[39] Levi-Montalcini R. The nerve growth factor 35years later. Science, 1987,237:1154-1162.
[40] Torcia M, Bracci-Laudiero L, Lucibello M, et al. Nerve growth factor is an autocrine survival factor for memory B lymphocytes. Cell, 1996,85:345-356.
[41] Gamci E, Caroleo M C, Aloe, L, et al. Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV. Proc Natl Acad Sci, 1999,96,14013-14018
[41] Aloe L, Simone M D, Properzi F. Nerve growth factor: a neurotrophin with activity on cells of the immune system. Microsc Res Tech, 1999,45:285-291.
[42] Marshall J S, Gomi K, Blennerhassett M G, et al. Nerve growth factor modifies the expression of inflammatory cytokines by mast cells via a prostanoid-dependent mechanism. J Immunol, 1999,162:4271-4276.
[43] Scholzen T, Armstrong C A, Bunnett N W, et al. Neuropeptides in the skin: interactions be,ween the neuroendocrine and skin immune systems. Exp Dermatol, 1998,7:81-96.
[44] Welker P, Grabbe J, Grutzkau A, et al. Effects of nerve growth factor(NGF) and other fibroblast-derived growth factors on immature human mast cells(HMC-1). Immunology, 1998,94:310-317.
[45] Weskamp G, Otten U. An enzyme-linked immunoassay for nerve growth factor(NGF): a tool for studying regulatory mechanisms involved in NGF production in
brain and in peripheral tissues. J Neurochem, 1987, 48:1779-1786.
[46] Woolf C J, Ma Q P, Allchome A, et al. Peripheral cell types contributing to the hyperalgesic action of nerve growth factor in inflammation. J Neurosci, 1996,16:2716-2723.
[47] Melchers F, Rolink A G, Schaniel C. The role of chemokines in regulating cell migration during humoral immune responses. Cell, 1999,99:351-354.
[48] Alcami A, Symons J A, Collins P D, et al. Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus. J Immunol, 1998,160:624-633.
[49] Graham K A, Lalani A S, Macen J L, et al. The T1/35kDa family of virus-infected tissues. Virology, 1997,229:12-24.
[50] Lalani A S, Ness T L, Singh R, et al. Functional comparisons among members of the poxvirus T1/35kDa family of soluble CC-chemokine inhibitor glycoproteins. Virology, 1998,250:173-184.
[51] Smith C A, Smith T D, Smolak P J, et al. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits β chemokine activity yet lacks sequence homology to known chemokine receptors. Virology, 1997,236:316-327.
[52] Damon I, Murphy P M, Moss B. Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine homolog. Proc Natl Acad Sci, 1998,95:6403-6407.
[53] Dairaghi D J, Fan R A, McMaster B E, et al. HHV8-encoded vMIP-Ⅰ selectively engages chemokine receptor CCR8. J Biol Chem, 1999,274:21569-21574.
[54] Endres M J, Garlisi C G, Xiao H, et al. The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine vMIP-Ⅰ is a specific agonist for the CC chemokine receptor(CCR)8. J Exp Med, 1999,189:1993-1998.
[55] Birkenbach M, Josefsen K, Yalamanchili R, et al. Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors. J Virol, 1993, 67:2209-2220.
[56] Schoneberg T, Schultz G, Gudermann T. Structural basis of G protein-coupled receptor function. Mol Cell Endocrinol, 1999,151: 181-193.
[57] Cao J X, Gershon P D, Black D N. Sequence analysis of HindⅢ Q2 fragment of capripoxvirus reveals a putative gene encoding a G-protein-coupled chemokine receptor homologue. Virology, 1995,209:207-212.
[58] Massung R F, Jayarama V, Moyer R W. DNA sequence analysis of conserved and unique regions of swinepox virus: identification of genetic elements supporting phenotypic observations including a novel G protein-coupled receptor homologue. Virology, 1993,197:511-528.
[59] Ahuja S K, Murphy P M. Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. J Biol Chem, 1993,268:20691-20694.
[60] Arvanitakis L, Geras-Raaka E, Varma A, Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature, 1997,385:347-350.
[61] Beisser P S, Grauls G, Bruggeman C A, et al. Deletion of the R78 G protein-coupled receptor gene from rat cytomegalovirus results in an attenuated, syncytium-inducing mutant strain. J Virol, 1999.,73:7218-7230.
[62] Gao J-L, Murphy PM. Human cytomegalovirus open reading frame US28 encodes a functional β chemokine receptor. J Biol Chem, 1994,269:28539-28542.
[63] Senkevich T G, Koonin E V, Bugert J J, et al. The genome of Molluscum contagiosum virus: analysis and comparison with other poxviruses. Virology, 1997, 233: 19-42.
[64] Xiang Y, Moss B. Identification of human and mouse homologs of the MC51L-53L-54L family of secreted glycoproteins encoded by the Molluscum contagiosum poxvirus. Virology, 1999,257:297-302.
[65] Xiang Y, Moss B. IL-18 binding and inhibition of interferon γ induction by human poxvirus encoded proteins. Proc Natl Acad Sci, 1999,96:1537-11542.
[66] Aizawa Y, Akita K, Taniai M, et al. Cloning and expression of interleukin-18 binding protein. FEBS Lett, 1999,445:338-342.
[67] Dao T, Ohashi K, Kayano T M. et al. Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells. Cell. Immunol, 1996,173:230-235.
[68] Dinarello C A. IL-18: a TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Imrnunol, 1999,103:11-24.
[69] Hyodo Y, Matsui K, NayashiN, et al. IL-I8 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor. J Immunol, 1999,162:1662-1668.
[70] Micallcf M J, Tanimoto T, Todgoc K, ct al. Simultancous exposure to interleukin-18 and interleukin-10 in vitro synergistically augments murinc spleen natural killer cell activity. Cancer Immunother, 1999, 8: 109-117.
[71] Takeda K, Tsutsui H, Yoshimoto T, et al. Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity, 1998,8:383-390.
[72] Tanaka-Kataoka, M, Kunikata T, Takayama S, et al. In vivo antiviral effect of interleukin 18 in a mouse model of vaccinia virus infection. Cytokine, 1999, 11:593-599.
[73] Turner P C, Moyer R W. Control of apoptosis by poxviruses. Semin Virol, 1998,8:453-469.
[74] Townsend A, Bastin J, Gould K, et al. Defective presentation to class Ⅰ-restricted cytotoxin T lymphotes in vaccinia-infected cells is overcome by enhanced degradation of antigen. J Exp Med, 1988,168:1211-1224.
[75] Smith G L, Chan Y S, Kerr S M. Transcriptional mapping and nucleotide sequence of a vaccinia virus gene encoding a polypeptide with extensive homology to DNA ligases. Nucleic Acids Res, 1989,17(22):9051-9062.
[76] Ensser A, Fleckenstein B. Alcelaphine herpesvirus type 1 has a semaphorin-like gene. J Gen Virol, 1995,76:1063-1067.
[77] Lange C, Liehr T, Goen M, et al. New eukaryotic semaphorins with close homology to semaphorins of DNA viruses. Genomics, 1998,51:340-350.
[78] Andrew M E, Coupar B E H. Biological effects of recombinant vaccinia virus-expressed interleukin 4. Cytokine,1992,4:281-286.
[79] Puehler F, Schwarz H, Waidner H, et al. An interferon-γ-binding protein of novel structure encoded by the fowlpox virus. J Biol Chem, 2003,278(9):6905-6911.
[80] 陈政良．C型凝集素的免疫功能．细胞与分子免疫学杂志，1977，13(2)：34-37．
[81] Fukuda M, Hiraoka N Yeh J-C. C-type lectins and sialyl Lewis X oligosaccharides: versatile roles in cell-cell interaction. J Cell Biol, 1999, 147:467-470.
[82] Ryan J C, Seaman W E. Divergent functions of lectin-like receptors on NK cells. Immunol Rev, 1997,155:79-89.
[83] Weis W I, Taylor M E, Drickamer K. The C-type lectin superfamily in the immune system. Immunol Rev, 1998,163:19-34.
[84] Neilan J G, Borca M V, Lu Z, et al. An African swine fever virus ORF with similarity to C-type lectins is non-essential for growth in swine macrophages in vitro and for virus virulence in domestic swine. J Gen Virol, 1999,80:2693-2697.
[85] Shchelkunov S N, Safronov P F, Totmenin A V, et al. The genome sequence analysis of the left and right species-specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins. Virology, 1998,243:432-460.
[86] Wilcock D, Duncan S A, Traktman P, et al. The vaccinia virus A40R gene product is a nonstructural, type Ⅱ membrane glycoprotein that is expressed at the cell surface. J Gen Virol, 1999,80:2137-2148.
[87] Barry M, McFadden G. Apoptosis regulators from DNA viruses. Curr Opin. Immunol, 1998,10: 422-430.
[88] Halford S, Wilson D I, Daw S C, et al. Isolation of a gene expressed during early embryogenesis from the region of 22q11 commonly deleted in DiGeorge syndrome. Hum Mol Genet, 1993,10:1577-1582.
[89] McFadden G, Graham K, Barry M. New strategies of immune modulation by DNA viruses. Transplant Proc, 1996,28:2085-2088.
[90] 金奇主编．医学分子病毒学．第一版．北京：科学出版社．2001．62-83．
[91] Gillard S, Spehner D, Drillien R. et al. Localization and sequence of a vaccinia virus gene required for multiplication in human cells. Proc Natl Acad. Sci, 1986,83:5573-5577.
[92] Ink B S, Gilbert C S, Evan G I. Delay of vaccinia virus-induced apoptosis in nonpermissive Chinese hamster ovary cells by the cowpox virus CHOhr and adenovirus EIB 19K genes. J Virol, 1995,69:661-668.
[93] Mossman K S, Lee F, Barry M. Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits. J Virol, 1996,70:4394-4410.
[94] Perkus M E, Goebel S J, Davis S W, et al. Vaccinia virus host range genes. Virology, 1990,179:276-286.
[95] Spehner D, Gillard S, Drillien R, et al. A cowpox virus gene required for multiplication in Chinese hamster ovary cells. J Virol, 1988, 62:1297-1304.
[96] Sutter G, Ramsey-Ewing A, Rosales R. et al. Stable expression of the vaccinia virus K1L gene in rabbit cells complements the host range defect of a vaccinia virus mutant. J Virol, 1994,68:4109-4116.
[97] Shchelkunov S N, Safronov P F, Totmenin A V, et al. The genome sequence analysis of the left and right species-specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins. Virology, 1998,243:432-460.
[98] Antoine G, Scheiflinger F, Dorner F, et al. The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses. Virology, 1998,244:365-396.
[99] Brick D J, Burke R D, Schiff L, et al. Shope fibroma virus RING finger protein N1R binds DNA and inhibits apoptosis. Virology, 1998,249:42-51.
[100] Senkevich T G, Koonin E V, Buller R M L. A poxvirus protein with a RING zinc finger motif is of crucial importance for virulence. Virology, 1994,198:118-128.
[101] Senkevich T G, Wolffe E J. Buller R M L. Ectromelia virus RING finger protein is localized in virus factories and is required for virus replication in macrophages. J Virol, 1995,69:4103-4111.
[2] Goebel S J, Johnson G P, Perkus M E, et al. The complete DNA sequence of vaccina virus. Virology, 1990,179:247-266,517-563.
[3] Boyle D B, Coupar E H. Construct of recombinant fowlpox viruses as vectors for poultry vaccines. Virus Res, 1988,10:343-356.
[4] Taylor J, Weinberg R, Languet B, et al. Recombinant fowlpox virus inducing protective immunity in non-avian species. Vaccine, 1988,6:497-503.
[5] Taylor J, Weinberg R, Kawaoka Y, et al. Protective immunity against avian influenza induced by a fowlpox virus recombinant. Vaccine, 1988,6:504-508.
[6] Afonso C L, Tulman E R, Lu Z, et al. The genome of fowlpox virus. J Virol, 2000,74:3815-3831.
[7] Laidlaw S M, Skinner M A. Comparison of the genome sequence of FP9, an attenuated, tissue culture-adapted European strain of Fowlpox virus, with those of virulent American and European viruses. J Gen Virol, 2004,85(2):305-322.
[8] 殷震，刘景华主编．动物病毒学．第二版．北京：科学出版社，1997．939-987．
[9] Buller R M, Palumbo G L. Poxvirus pathogenesis. Microbiological review, 1991,55(1):80-122.
[10] 徐耀先，周晓峰，刘立德主编．分子病毒学．第一版．武汉：湖北科学技术出版社，2000．253-264．
[11] Boulanger D, Smith T, Skinner M A. Morphogenesis and release of fowlpox virus. J Gen Virol, 2000, 81:675-687.
[12] 卡尔尼克B W主编，高福等译．禽病学．第十版．北京：北京农业出版社，2000．653-659．
[13] Baxby D, Paoletti E. Potential use of non-replicating vector as recombinant vaccines. Vaccine, 1992,10(1):8-9.
[14] Fatunmbi O F, Reed, R M. Evaluation of a commercial modified live virus fowl pox vaccine for the control of 'variant' fowl poxvirus infections, Avian Dis,1996, 40: 582-587.
[15] Tadese T, Reed W M. Detection of specific reticuloendotheliosis virus sequence and protein from REV-integrated fowlpox virus swains. J Virol Methods, 2003,110(1):99-104.
[16] Singh P, Schnitzlein W M, Tripathy D N. Reticuloendotheliosis Virus Sequences within the Genomes of Field Strains of Fowlpox Virus Display Variability. J Virol, 2003,77(10):5855-5862.
[17] Gubser C, Hue S, Kellam P, et al. Poxvirus genomes: a phylogenetic analysis. J Gen Virol, 2004, 85(1):105-117.
[18] Coupar, B E H, Teo T, Boyle D B. Restriction endonuclease mapping of the fowlpox virus genome. Virology, 1990,179:159-167.
[19] Mockett B, Binns M M, Boursnell M E G., et al. Comparison of the locations of homologgus fowlpox and vaccinia virus genes reveals major genome reorganization. J Gen Virol, 1992, 73: 2661-2668.
[20] Campbell J I A, Binns M M, Tomley F M, et al. Tandem repeated sequences within the terminal region of the fowlpox virus genome. J Gen Virol, 1989,210:771-784.
[21] Coupar B E H, Teo T, Boyle D B. Restriction endonuclease mapping of the fowlpox virus genome. Virology, 1990,179:159-167.
[22] Goebel S J, Johnson G P M, Perkus E, et al. The complete DNA sequence of vaccinia virus. Virology, 1990, 179:247-266.
[23] Massung R F, Liu L I, Qi J, et al. Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975. Virology, 1994,201:215-240.
[24] Senkevich T G, Koonin E V, Bugert J J, et al. The genome of Molluscum contagiosum virus: analysis and comparison with other poxviruses. Virology, 1997,233:19-42.
[25] Massung R F, Esposito J J, Liu L I, et al. Potential virulence determinants in terminal regions of variola smallpox virus genome. Nature, 1993,366:748-751.
[26] Senkevich T G, Bugert J J, Sisler J R, et al. Genome sequence of a human tumorigenic poxvirus: prediction of specific host response-evasion genes. Science, 1996,273:813-816.
[27] 金宁一，殷震．痘苗病毒载体研究进展．生物化学与生物物理进展，1996，23(4)：301-304．
[28] 顾万钧，金宁一．鸡痘病毒载体研究进展．吉林农业大学学报，1995，17(4)：89-95．
[29] 王志亮，刘秀梵．禽痘病毒分子生物学．中国动物检疫，1996，13(4)：31-33．
[30] Davison A J, Moss B. Structure of vaccinia virus early promotor. J Virol, 1989. 210:749-769.
[31] Kumar S, Boyle D B. Mapping of a major early/late gene of fowlpox virus. Virus Res,1990,15:175-185.
[32] Kumar S, Boyle D B. A poxvirus bidirectional promoter element with early/late and late functions. Virology, 1990,179:151-158.
[33] Zantinge J L, Krell P J, Derbyshire J B. Partial transcriptional mapping of the fowlpox virus genome and analysis of the EcoRI L fragment. J Gen Virol, 1996,77:603-614.
[34] Golini F, Kates J R. Transcriptional and translational analysis of a strongly
expressed early region of the vaccinia virus. J Virol, 1984,49(2):459-470.
[35] Ahn B, Moss B. Capped poly(A) leader of variable lengths at the ends of vaccinia virus late mRNA. J Virol, 1989,63(1)226-232.
[36] Boulanger D, Green P, Jones B, et al. Identification and characterization of three immunodominant structure proteins of fowlpox virus. J Virol, 2002,76(19):9844-9855.
[37] 余传霖，熊思东主编．分子免疫学．第一版．上海：复旦大学出版社／上海医科大学出版社，2001．815-825．
[38] Bradshaw R A, Blundell T L, Lapatto R, et al. Nerve growth factor revisited. Trends Biochem Sci,1993,18:48-52.
[39] Levi-Montalcini R. The nerve growth factor 35years later. Science, 1987,237:1154-1162.
[40] Torcia M, Bracci-Laudiero L, Lucibello M, et al. Nerve growth factor is an autocrine survival factor for memory B lymphocytes. Cell, 1996,85:345-356.
[41] Gamci E, Caroleo M C, Aloe, L, et al. Nerve growth factor is an autocrine factor essential for the survival of macrophages infected with HIV. Proc Natl Acad Sci, 1999,96,14013-14018
[41] Aloe L, Simone M D, Properzi F. Nerve growth factor: a neurotrophin with activity on cells of the immune system. Microsc Res Tech, 1999,45:285-291.
[42] Marshall J S, Gomi K, Blennerhassett M G, et al. Nerve growth factor modifies the expression of inflammatory cytokines by mast cells via a prostanoid-dependent mechanism. J Immunol, 1999,162:4271-4276.
[43] Scholzen T, Armstrong C A, Bunnett N W, et al. Neuropeptides in the skin: interactions be,ween the neuroendocrine and skin immune systems. Exp Dermatol, 1998,7:81-96.
[44] Welker P, Grabbe J, Grutzkau A, et al. Effects of nerve growth factor(NGF) and other fibroblast-derived growth factors on immature human mast cells(HMC-1). Immunology, 1998,94:310-317.
[45] Weskamp G, Otten U. An enzyme-linked immunoassay for nerve growth factor(NGF): a tool for studying regulatory mechanisms involved in NGF production in
brain and in peripheral tissues. J Neurochem, 1987, 48:1779-1786.
[46] Woolf C J, Ma Q P, Allchome A, et al. Peripheral cell types contributing to the hyperalgesic action of nerve growth factor in inflammation. J Neurosci, 1996,16:2716-2723.
[47] Melchers F, Rolink A G, Schaniel C. The role of chemokines in regulating cell migration during humoral immune responses. Cell, 1999,99:351-354.
[48] Alcami A, Symons J A, Collins P D, et al. Blockade of chemokine activity by a soluble chemokine binding protein from vaccinia virus. J Immunol, 1998,160:624-633.
[49] Graham K A, Lalani A S, Macen J L, et al. The T1/35kDa family of virus-infected tissues. Virology, 1997,229:12-24.
[50] Lalani A S, Ness T L, Singh R, et al. Functional comparisons among members of the poxvirus T1/35kDa family of soluble CC-chemokine inhibitor glycoproteins. Virology, 1998,250:173-184.
[51] Smith C A, Smith T D, Smolak P J, et al. Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits β chemokine activity yet lacks sequence homology to known chemokine receptors. Virology, 1997,236:316-327.
[52] Damon I, Murphy P M, Moss B. Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine homolog. Proc Natl Acad Sci, 1998,95:6403-6407.
[53] Dairaghi D J, Fan R A, McMaster B E, et al. HHV8-encoded vMIP-Ⅰ selectively engages chemokine receptor CCR8. J Biol Chem, 1999,274:21569-21574.
[54] Endres M J, Garlisi C G, Xiao H, et al. The Kaposi's sarcoma-related herpesvirus (KSHV)-encoded chemokine vMIP-Ⅰ is a specific agonist for the CC chemokine receptor(CCR)8. J Exp Med, 1999,189:1993-1998.
[55] Birkenbach M, Josefsen K, Yalamanchili R, et al. Epstein-Barr virus-induced genes: first lymphocyte-specific G protein-coupled peptide receptors. J Virol, 1993, 67:2209-2220.
[56] Schoneberg T, Schultz G, Gudermann T. Structural basis of G protein-coupled receptor function. Mol Cell Endocrinol, 1999,151: 181-193.
[57] Cao J X, Gershon P D, Black D N. Sequence analysis of HindⅢ Q2 fragment of capripoxvirus reveals a putative gene encoding a G-protein-coupled chemokine receptor homologue. Virology, 1995,209:207-212.
[58] Massung R F, Jayarama V, Moyer R W. DNA sequence analysis of conserved and unique regions of swinepox virus: identification of genetic elements supporting phenotypic observations including a novel G protein-coupled receptor homologue. Virology, 1993,197:511-528.
[59] Ahuja S K, Murphy P M. Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. J Biol Chem, 1993,268:20691-20694.
[60] Arvanitakis L, Geras-Raaka E, Varma A, Human herpesvirus KSHV encodes a constitutively active G-protein-coupled receptor linked to cell proliferation. Nature, 1997,385:347-350.
[61] Beisser P S, Grauls G, Bruggeman C A, et al. Deletion of the R78 G protein-coupled receptor gene from rat cytomegalovirus results in an attenuated, syncytium-inducing mutant strain. J Virol, 1999.,73:7218-7230.
[62] Gao J-L, Murphy PM. Human cytomegalovirus open reading frame US28 encodes a functional β chemokine receptor. J Biol Chem, 1994,269:28539-28542.
[63] Senkevich T G, Koonin E V, Bugert J J, et al. The genome of Molluscum contagiosum virus: analysis and comparison with other poxviruses. Virology, 1997, 233: 19-42.
[64] Xiang Y, Moss B. Identification of human and mouse homologs of the MC51L-53L-54L family of secreted glycoproteins encoded by the Molluscum contagiosum poxvirus. Virology, 1999,257:297-302.
[65] Xiang Y, Moss B. IL-18 binding and inhibition of interferon γ induction by human poxvirus encoded proteins. Proc Natl Acad Sci, 1999,96:1537-11542.
[66] Aizawa Y, Akita K, Taniai M, et al. Cloning and expression of interleukin-18 binding protein. FEBS Lett, 1999,445:338-342.
[67] Dao T, Ohashi K, Kayano T M. et al. Interferon-gamma-inducing factor, a novel cytokine, enhances Fas ligand-mediated cytotoxicity of murine T helper 1 cells. Cell. Immunol, 1996,173:230-235.
[68] Dinarello C A. IL-18: a TH1-inducing, proinflammatory cytokine and new member of the IL-1 family. J Allergy Clin Imrnunol, 1999,103:11-24.
[69] Hyodo Y, Matsui K, NayashiN, et al. IL-I8 up-regulates perforin-mediated NK activity without increasing perforin messenger RNA expression by binding to constitutively expressed IL-18 receptor. J Immunol, 1999,162:1662-1668.
[70] Micallcf M J, Tanimoto T, Todgoc K, ct al. Simultancous exposure to interleukin-18 and interleukin-10 in vitro synergistically augments murinc spleen natural killer cell activity. Cancer Immunother, 1999, 8: 109-117.
[71] Takeda K, Tsutsui H, Yoshimoto T, et al. Defective NK cell activity and Th1 response in IL-18-deficient mice. Immunity, 1998,8:383-390.
[72] Tanaka-Kataoka, M, Kunikata T, Takayama S, et al. In vivo antiviral effect of interleukin 18 in a mouse model of vaccinia virus infection. Cytokine, 1999, 11:593-599.
[73] Turner P C, Moyer R W. Control of apoptosis by poxviruses. Semin Virol, 1998,8:453-469.
[74] Townsend A, Bastin J, Gould K, et al. Defective presentation to class Ⅰ-restricted cytotoxin T lymphotes in vaccinia-infected cells is overcome by enhanced degradation of antigen. J Exp Med, 1988,168:1211-1224.
[75] Smith G L, Chan Y S, Kerr S M. Transcriptional mapping and nucleotide sequence of a vaccinia virus gene encoding a polypeptide with extensive homology to DNA ligases. Nucleic Acids Res, 1989,17(22):9051-9062.
[76] Ensser A, Fleckenstein B. Alcelaphine herpesvirus type 1 has a semaphorin-like gene. J Gen Virol, 1995,76:1063-1067.
[77] Lange C, Liehr T, Goen M, et al. New eukaryotic semaphorins with close homology to semaphorins of DNA viruses. Genomics, 1998,51:340-350.
[78] Andrew M E, Coupar B E H. Biological effects of recombinant vaccinia virus-expressed interleukin 4. Cytokine,1992,4:281-286.
[79] Puehler F, Schwarz H, Waidner H, et al. An interferon-γ-binding protein of novel structure encoded by the fowlpox virus. J Biol Chem, 2003,278(9):6905-6911.
[80] 陈政良．C型凝集素的免疫功能．细胞与分子免疫学杂志，1977，13(2)：34-37．
[81] Fukuda M, Hiraoka N Yeh J-C. C-type lectins and sialyl Lewis X oligosaccharides: versatile roles in cell-cell interaction. J Cell Biol, 1999, 147:467-470.
[82] Ryan J C, Seaman W E. Divergent functions of lectin-like receptors on NK cells. Immunol Rev, 1997,155:79-89.
[83] Weis W I, Taylor M E, Drickamer K. The C-type lectin superfamily in the immune system. Immunol Rev, 1998,163:19-34.
[84] Neilan J G, Borca M V, Lu Z, et al. An African swine fever virus ORF with similarity to C-type lectins is non-essential for growth in swine macrophages in vitro and for virus virulence in domestic swine. J Gen Virol, 1999,80:2693-2697.
[85] Shchelkunov S N, Safronov P F, Totmenin A V, et al. The genome sequence analysis of the left and right species-specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins. Virology, 1998,243:432-460.
[86] Wilcock D, Duncan S A, Traktman P, et al. The vaccinia virus A40R gene product is a nonstructural, type Ⅱ membrane glycoprotein that is expressed at the cell surface. J Gen Virol, 1999,80:2137-2148.
[87] Barry M, McFadden G. Apoptosis regulators from DNA viruses. Curr Opin. Immunol, 1998,10: 422-430.
[88] Halford S, Wilson D I, Daw S C, et al. Isolation of a gene expressed during early embryogenesis from the region of 22q11 commonly deleted in DiGeorge syndrome. Hum Mol Genet, 1993,10:1577-1582.
[89] McFadden G, Graham K, Barry M. New strategies of immune modulation by DNA viruses. Transplant Proc, 1996,28:2085-2088.
[90] 金奇主编．医学分子病毒学．第一版．北京：科学出版社．2001．62-83．
[91] Gillard S, Spehner D, Drillien R. et al. Localization and sequence of a vaccinia virus gene required for multiplication in human cells. Proc Natl Acad. Sci, 1986,83:5573-5577.
[92] Ink B S, Gilbert C S, Evan G I. Delay of vaccinia virus-induced apoptosis in nonpermissive Chinese hamster ovary cells by the cowpox virus CHOhr and adenovirus EIB 19K genes. J Virol, 1995,69:661-668.
[93] Mossman K S, Lee F, Barry M. Disruption of M-T5, a novel myxoma virus gene member of poxvirus host range superfamily, results in dramatic attenuation of myxomatosis in infected European rabbits. J Virol, 1996,70:4394-4410.
[94] Perkus M E, Goebel S J, Davis S W, et al. Vaccinia virus host range genes. Virology, 1990,179:276-286.
[95] Spehner D, Gillard S, Drillien R, et al. A cowpox virus gene required for multiplication in Chinese hamster ovary cells. J Virol, 1988, 62:1297-1304.
[96] Sutter G, Ramsey-Ewing A, Rosales R. et al. Stable expression of the vaccinia virus K1L gene in rabbit cells complements the host range defect of a vaccinia virus mutant. J Virol, 1994,68:4109-4116.
[97] Shchelkunov S N, Safronov P F, Totmenin A V, et al. The genome sequence analysis of the left and right species-specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins. Virology, 1998,243:432-460.
[98] Antoine G, Scheiflinger F, Dorner F, et al. The complete genomic sequence of the modified vaccinia Ankara strain: comparison with other orthopoxviruses. Virology, 1998,244:365-396.
[99] Brick D J, Burke R D, Schiff L, et al. Shope fibroma virus RING finger protein N1R binds DNA and inhibits apoptosis. Virology, 1998,249:42-51.
[100] Senkevich T G, Koonin E V, Buller R M L. A poxvirus protein with a RING zinc finger motif is of crucial importance for virulence. Virology, 1994,198:118-128.
[101] Senkevich T G, Wolffe E J. Buller R M L. Ectromelia virus RING finger protein is localized in virus factories and is required for virus replication in macrophages. J Virol, 1995,69:4103-4111.