禽流感病毒非结构蛋白与宿主相关蛋白相互作用及感染鸡组织病理学研究
|
摘要
禽流感(Avian Influenza,AI)是由禽流感病毒(Avian Influenza Virus,AIV)引起的一种禽类感染和/或疾病综合征,被世界动物卫生组织(OIE)和我国定为A类传染病。自1878年首次在意大利暴发以来,已在世界各地广泛流行。近年来,AI出现了新特点,尤其是高致病性禽流感病毒(HPAIV)通过抗原漂移和抗原转变,已获得了感染人并造成死亡的能力,这赋予了HPAIV更重要的公共卫生学意义。
目前,AIV致病机制还不甚清楚,可能是多基因共同作用的结果。其中,非结构蛋白(Non-structural protein,NS1)只存在于病毒感染的细胞内,是在细胞水平上的调节AIV致病性的关键因子。NS1蛋白主要是通过其RNA结合区和效应区与宿主内的许多蛋白相互作用来实现的,但这些研究大多数是采用人流感及其适应性细胞来研究的,而利用AIV及其天然宿主的研究还未见报道。因此,深入开展HPAIV的NS1蛋白与其天然宿主蛋白之间的相互作用研究,可进一步揭示NS1蛋白的功能及其调节HPAIV致病力的机制。因此,本研究利用HPAIV及SPF鸡为实验材料,运用组织病理学及蛋白质相互作用技术,研究了SPF鸡感染AIV的细胞凋亡、NS1蛋白的分布及NSl蛋白的相互作用蛋白,取得了如下成果:
1 H9N2亚型AIV NSl基因的遗传进化分析
利用RT-PCR方法,扩增了1998-2005年间分离的9株H9N2亚型AIV的NS1基因,序列分析表明,9株AIV NS1基因完整的阅读框均为654bp,编码217个氨基酸,其核苷酸及其推导氨基酸同源性分别为95.4%-99.8%和93.6%-100%;9株病毒的NS1蛋白的C-端均缺失了13个aa,已成为中国大陆分离株(H9N2亚型)的一个分子标记。进化分析表明,所有分离株都属于基因A群,形成了一个独立分支,且均起源于中国最早的分离株(Ck/BJ/1/94株),说明H9N2亚型AIV的NS1基因随着流行时间出现了分化。另外,除Ck/HN/A3/98株外其余8株属于Ck/SH/F/98-like,这说明了Ck/SH/F/98-like株的H9N2亚型AIV在中国大陆鸡群中广泛存在。
2 SPF鸡感染高致病性禽流感病毒(H5N1亚型)细胞凋亡的研究
用末端转移酶介导的缺口末端标记法(TdT-mediated X-dUTP nick end labling,TUNEL)研究了SPF鸡人工感染HPAIV(H5N1亚型)的细胞凋亡,结果表明,HPAIV(H5N1亚型)能诱导各脏器不同程度的细胞凋亡,以胸腺、法氏囊、胰脏、肾脏的细胞凋亡最严重,凋亡细胞主要为血管内皮细胞、腺上皮细胞、软骨细胞及部分淋巴细胞。本研究表明,HPAIV可诱导本动物发生快速的细胞凋亡。
3 HPAIV(H5N1亚型)NS1蛋白在感染鸡组织中分布研究
利用NS1蛋白单克隆抗体,建立了检测NS1蛋白的免疫组化法(SABC法),并研究了HPAIV感染30-31h后NS1蛋白在鸡各脏器中的分布,结果表明,NS1蛋白主要分布于心脏、胰脏、肾脏及小脑颗粒层;阳性细胞主要为各组织器官的小或微血管内皮细胞、心肌细胞、肾小管上皮细胞、腺上皮细胞、部分淋巴细胞及坏死灶周围的细胞,说明了心肌、胰腺、肾脏、小脑及血管内皮细胞可能是HPAIV的主要靶器官。结合细胞凋亡的研究结果,可推测,心血管系统在HPAIV的复制和扩散中起重要作用。同时也证明了NS1蛋白与细胞凋亡有相关性。
4利用酵母双杂交系统筛选NS1蛋白相互作用的宿主蛋白
本研究利用SMART技术首次构建了HPAIV感染鸡脾脏cDNA文库,然后利用酵母双杂交系统从该cDNA文库中初步筛选到了4个能与NS1蛋白相互作用的蛋白,序列测定和Blast分析表明,4个基因分别为鸡源ISG12-2、IRF2、PPM1F及AIV的M蛋白,其中ISG12-2和IRF2基因含完整阅读框。推测,NS1蛋白可能是通过调节干扰素的产生、自身磷酸化及调节病毒复制等方式来发挥其调节AIV致病力的功能。这些蛋白的获得,进一步解释了NS1蛋白在调节HPAIV致病性方面的作用,同时也为HPAIV感染人的机制提供了有意义的参考。
5利用细菌双杂交系统和GST融合蛋白沉降技术验证NS1蛋白与ISG12-2和IRF2蛋白的相互作用
本研究利用细菌双杂交系统和GST融合蛋白沉降技术进一步验证NS1蛋白分别与ISG12-2及IRF2蛋白的相互作用,结果表明,在体内和体外,NS1蛋白与ISG12-2及IRF2蛋白间存在相互作用。NS1蛋白与ISG12-2和IRF2的相互作用,可能抑制某些IFN表达相关通路,拮抗IFN的表达,降低机体的抗病毒状态,利于AIV的复制和扩散。
Avian influenza(AI) is a fatal syndrome of avian caused by avian influenza virus (AIV),characterized either by the general or respiratory disease,which was defined as the type A infectious disease by OIE.Since the first breakout in Italy in 1887,AIVs have occured worldwide in avian-raising countries.For the past few years,some new characters of AIV have appeared,especially for highly pathogenic avian influenza viruses(HPAIV).Antigen shift or drift has appeared easily for HPAIV,which can make the HPAIV obtain the capability to infection and make the human death,such as in HongKong and Southeast Asia.So HPAIV is more important for the public hygieology.
At present,the pathogenic mechanism of AIV in chicken has been still not clear, which maybe the common results of more than one gene.Hemagglutinin(HA)、Neuraminidase(NA) and Non-structural protein(NS1)were more important in the all genes of AIV.HA and NA are the key factors for the subtype、antigen variation and pathogenic regulation during influenza virus infection.It has been reported that the NS1 protein,a non-structural protein of the type A influenza virus,can interact with the host cell proteins in vitro via its RNA-binding domain and effector domain,By the protein-protein interaction,NS1 protein can shutoff the host cellular protein synthesis, antagonize the alpha/beta interferon(IFN-α/β) system,induce apoptosis and regulate the viral protein expression.So NS1 protein is an important virulence factor which decides a great damage to host cells on the cell level.Those researches about NS1 Protein were mostly carried out using the human influenza virus and its suitable cell line,but not the avian influenza virus and its natural host(chicken).To elucidate the interaction between NS1 protein and natural host(chicken) protein is not only significant to understand the function of NS1 protein and how to regulate the virulence,but also helpful for preventing and curing the infection of AIV.
In present study,the histopathology method and protein-protein interaction technology were applied to study on the pathology of H5NI AIV strain on both cellular and protein level in order to document the reason why the chicken is dead shortly.The results were reported as follow:
1.Genetic analysis of the NS1 Genes of H9N2 Influenza Viruses
The nonstructural genes(NS1) of nine H9N2 subtype influenza viruses isolated from diseased chickens on different farms during1998-2005 were amplified by RT-PCR and completely sequenced.The nucleotide and deduced amino acid sequences of NS1 genes of these isolates were analysis and compared.The results showed that NS1 gene of all H9N2 isolates contained 654 bp and encoded 217 amino acids.The homologies of the nucleotide and deduced amino acid of the isolates were 95.4%-99.8%and 93.6%-100%, respectively.Comparison of the amino acid sequences of NS1 proteins of these isolates with other H9N2 viruses demonstrated that NS1 proteins of the nine strains had a deletion of 13 amino acid residues at the carboxy terminus,which may be the molecule mark of the isolates in mainland China.Phylogenetic analysis revealed that the NS1 genes of these isolates fell into the same lineage and belonged to allele A.The other eight isolates belonged to the Ck/SH/F/98-1ike lineage except Ck/HN/A3/98 strain,but all the isolates derived from Ck/BJ/1/94 strain firstly isolated from mainland China in 1994.The result indicated that H9N2 subtype AIV appear differentiation following the time and the viruses belonging to Ck/SH/F/98-like acquired an epidemiological advantage in chicken population in mainland China.
2.Study on the apoptosis of SPF chicken challenged with HPAIV(H5N1 subtype)
The study on the apoptosis of dead SPF chicken challenged with HPAIV(H5N1 subtype) was carried out using the TdT-mediated X-dUTP nick end labling method (TUNEL) The results documented that HPAIV could induce the different apoptosis in different organs or tissues.The apoptosis in Thymus、Bursa of Fabricius、Pancreas and Kindey was more severe than the other organs or tissues.The apoptosis cells included the vascular endothelial cells,glandular epithelium cartilage corpuscle and lympholeukocyte. According to the researches about the apoptosis,it was deduced that the apoptosis, shortly happened to the chicken incubated with HPAIV,maybe the mechanism which causes the chicken death quickly.
3.Study on the distribution of NS1 protein in the different organs of infected chicken
The monoclonal antibody of NS1 protein was applied to develop the immunohistochemistry method(SABC method) in order to detect the NS1 protein.The study on the distribution of NS1 protein was detected in the different organs of chicken infected with HPAIV after 30-31hours.The main organs which can detect the positive signal of NS1 protein was the heart、pancreas、kidney and cerebellum granular layer.The positive signals were stronger than the others.The positive cells were involved in small or microvascular endotheliocyte、myocardial cell、renal tubular epithelial cell、glandular epithelium and epithelium.The results illustrated that the heart、pancreas、kidney cerebellum and microvascular endotheliocyte may be the main target organs in which HPAIV can duplicated effectively and product many effective virion.In this present study,It was presumed that the cardiovascular system was important for the duplication and diffusion of AIV.At the same time,the obvious associativity between the NS1 protein and apotosis was proved.
4.Screening and identification of host protein interacted with NS1 protein using the yeast two hybrid system
In present study,spleen cDNA library of chicken incubated with HPAIV(H5N1 subtype) was firstly constructed using the switching mechanism at 5′end of RNA transcript technology.Four proteins which can interact with NS1 protein were screened from this cDNA library using the yeast two hybrid system(Y2H).These proteins included the chicken interferon-stimulated gene12-2(ISG12-2),interferon regulatory factor 2(IRF2),Protein phosphatase 1F(PPM1F) and M protein of AIV.The interaction between NS1 protein and ISG12-2 and IRF2 was identified,both in vitro and in vivo,by bacteria two-hybrid system and GST fusion proteins sedimentation technology, respectively.It was deduced that some signal pathway associated with IFN expression may be inhibited by the protein-protein interaction,which would affect the expression of IFN and degress the IFN-mediated antiviral responses.The results would explain the function of NS1 protein and how to regulate the pathogenicity.These studies also will give some reference to the mechanism which HPAIV infects human being.
5.Identification of the interaction between NS1 protein and ISG12-2 or IRF2 using the bacterial two hybrid system and GST pull-down test
In this study,the interactons between NS1 protein with ISG12-2 and IRF2 protein were further identified using the bacterial two hybrid system and GST pull-down test,respectively.The results showed that NS1 protein interacted with ISG12-2 and IRF2 protein in vivo and in vitro.It was presumed that some pathways associated with the expressing of interferon were blocked and the expressing of interferon was inhibited by the interactions,which degraded the antivirus immune response and was beneficial for the duplication and diffusion of AIV.
目前,AIV致病机制还不甚清楚,可能是多基因共同作用的结果。其中,非结构蛋白(Non-structural protein,NS1)只存在于病毒感染的细胞内,是在细胞水平上的调节AIV致病性的关键因子。NS1蛋白主要是通过其RNA结合区和效应区与宿主内的许多蛋白相互作用来实现的,但这些研究大多数是采用人流感及其适应性细胞来研究的,而利用AIV及其天然宿主的研究还未见报道。因此,深入开展HPAIV的NS1蛋白与其天然宿主蛋白之间的相互作用研究,可进一步揭示NS1蛋白的功能及其调节HPAIV致病力的机制。因此,本研究利用HPAIV及SPF鸡为实验材料,运用组织病理学及蛋白质相互作用技术,研究了SPF鸡感染AIV的细胞凋亡、NS1蛋白的分布及NSl蛋白的相互作用蛋白,取得了如下成果:
1 H9N2亚型AIV NSl基因的遗传进化分析
利用RT-PCR方法,扩增了1998-2005年间分离的9株H9N2亚型AIV的NS1基因,序列分析表明,9株AIV NS1基因完整的阅读框均为654bp,编码217个氨基酸,其核苷酸及其推导氨基酸同源性分别为95.4%-99.8%和93.6%-100%;9株病毒的NS1蛋白的C-端均缺失了13个aa,已成为中国大陆分离株(H9N2亚型)的一个分子标记。进化分析表明,所有分离株都属于基因A群,形成了一个独立分支,且均起源于中国最早的分离株(Ck/BJ/1/94株),说明H9N2亚型AIV的NS1基因随着流行时间出现了分化。另外,除Ck/HN/A3/98株外其余8株属于Ck/SH/F/98-like,这说明了Ck/SH/F/98-like株的H9N2亚型AIV在中国大陆鸡群中广泛存在。
2 SPF鸡感染高致病性禽流感病毒(H5N1亚型)细胞凋亡的研究
用末端转移酶介导的缺口末端标记法(TdT-mediated X-dUTP nick end labling,TUNEL)研究了SPF鸡人工感染HPAIV(H5N1亚型)的细胞凋亡,结果表明,HPAIV(H5N1亚型)能诱导各脏器不同程度的细胞凋亡,以胸腺、法氏囊、胰脏、肾脏的细胞凋亡最严重,凋亡细胞主要为血管内皮细胞、腺上皮细胞、软骨细胞及部分淋巴细胞。本研究表明,HPAIV可诱导本动物发生快速的细胞凋亡。
3 HPAIV(H5N1亚型)NS1蛋白在感染鸡组织中分布研究
利用NS1蛋白单克隆抗体,建立了检测NS1蛋白的免疫组化法(SABC法),并研究了HPAIV感染30-31h后NS1蛋白在鸡各脏器中的分布,结果表明,NS1蛋白主要分布于心脏、胰脏、肾脏及小脑颗粒层;阳性细胞主要为各组织器官的小或微血管内皮细胞、心肌细胞、肾小管上皮细胞、腺上皮细胞、部分淋巴细胞及坏死灶周围的细胞,说明了心肌、胰腺、肾脏、小脑及血管内皮细胞可能是HPAIV的主要靶器官。结合细胞凋亡的研究结果,可推测,心血管系统在HPAIV的复制和扩散中起重要作用。同时也证明了NS1蛋白与细胞凋亡有相关性。
4利用酵母双杂交系统筛选NS1蛋白相互作用的宿主蛋白
本研究利用SMART技术首次构建了HPAIV感染鸡脾脏cDNA文库,然后利用酵母双杂交系统从该cDNA文库中初步筛选到了4个能与NS1蛋白相互作用的蛋白,序列测定和Blast分析表明,4个基因分别为鸡源ISG12-2、IRF2、PPM1F及AIV的M蛋白,其中ISG12-2和IRF2基因含完整阅读框。推测,NS1蛋白可能是通过调节干扰素的产生、自身磷酸化及调节病毒复制等方式来发挥其调节AIV致病力的功能。这些蛋白的获得,进一步解释了NS1蛋白在调节HPAIV致病性方面的作用,同时也为HPAIV感染人的机制提供了有意义的参考。
5利用细菌双杂交系统和GST融合蛋白沉降技术验证NS1蛋白与ISG12-2和IRF2蛋白的相互作用
本研究利用细菌双杂交系统和GST融合蛋白沉降技术进一步验证NS1蛋白分别与ISG12-2及IRF2蛋白的相互作用,结果表明,在体内和体外,NS1蛋白与ISG12-2及IRF2蛋白间存在相互作用。NS1蛋白与ISG12-2和IRF2的相互作用,可能抑制某些IFN表达相关通路,拮抗IFN的表达,降低机体的抗病毒状态,利于AIV的复制和扩散。
Avian influenza(AI) is a fatal syndrome of avian caused by avian influenza virus (AIV),characterized either by the general or respiratory disease,which was defined as the type A infectious disease by OIE.Since the first breakout in Italy in 1887,AIVs have occured worldwide in avian-raising countries.For the past few years,some new characters of AIV have appeared,especially for highly pathogenic avian influenza viruses(HPAIV).Antigen shift or drift has appeared easily for HPAIV,which can make the HPAIV obtain the capability to infection and make the human death,such as in HongKong and Southeast Asia.So HPAIV is more important for the public hygieology.
At present,the pathogenic mechanism of AIV in chicken has been still not clear, which maybe the common results of more than one gene.Hemagglutinin(HA)、Neuraminidase(NA) and Non-structural protein(NS1)were more important in the all genes of AIV.HA and NA are the key factors for the subtype、antigen variation and pathogenic regulation during influenza virus infection.It has been reported that the NS1 protein,a non-structural protein of the type A influenza virus,can interact with the host cell proteins in vitro via its RNA-binding domain and effector domain,By the protein-protein interaction,NS1 protein can shutoff the host cellular protein synthesis, antagonize the alpha/beta interferon(IFN-α/β) system,induce apoptosis and regulate the viral protein expression.So NS1 protein is an important virulence factor which decides a great damage to host cells on the cell level.Those researches about NS1 Protein were mostly carried out using the human influenza virus and its suitable cell line,but not the avian influenza virus and its natural host(chicken).To elucidate the interaction between NS1 protein and natural host(chicken) protein is not only significant to understand the function of NS1 protein and how to regulate the virulence,but also helpful for preventing and curing the infection of AIV.
In present study,the histopathology method and protein-protein interaction technology were applied to study on the pathology of H5NI AIV strain on both cellular and protein level in order to document the reason why the chicken is dead shortly.The results were reported as follow:
1.Genetic analysis of the NS1 Genes of H9N2 Influenza Viruses
The nonstructural genes(NS1) of nine H9N2 subtype influenza viruses isolated from diseased chickens on different farms during1998-2005 were amplified by RT-PCR and completely sequenced.The nucleotide and deduced amino acid sequences of NS1 genes of these isolates were analysis and compared.The results showed that NS1 gene of all H9N2 isolates contained 654 bp and encoded 217 amino acids.The homologies of the nucleotide and deduced amino acid of the isolates were 95.4%-99.8%and 93.6%-100%, respectively.Comparison of the amino acid sequences of NS1 proteins of these isolates with other H9N2 viruses demonstrated that NS1 proteins of the nine strains had a deletion of 13 amino acid residues at the carboxy terminus,which may be the molecule mark of the isolates in mainland China.Phylogenetic analysis revealed that the NS1 genes of these isolates fell into the same lineage and belonged to allele A.The other eight isolates belonged to the Ck/SH/F/98-1ike lineage except Ck/HN/A3/98 strain,but all the isolates derived from Ck/BJ/1/94 strain firstly isolated from mainland China in 1994.The result indicated that H9N2 subtype AIV appear differentiation following the time and the viruses belonging to Ck/SH/F/98-like acquired an epidemiological advantage in chicken population in mainland China.
2.Study on the apoptosis of SPF chicken challenged with HPAIV(H5N1 subtype)
The study on the apoptosis of dead SPF chicken challenged with HPAIV(H5N1 subtype) was carried out using the TdT-mediated X-dUTP nick end labling method (TUNEL) The results documented that HPAIV could induce the different apoptosis in different organs or tissues.The apoptosis in Thymus、Bursa of Fabricius、Pancreas and Kindey was more severe than the other organs or tissues.The apoptosis cells included the vascular endothelial cells,glandular epithelium cartilage corpuscle and lympholeukocyte. According to the researches about the apoptosis,it was deduced that the apoptosis, shortly happened to the chicken incubated with HPAIV,maybe the mechanism which causes the chicken death quickly.
3.Study on the distribution of NS1 protein in the different organs of infected chicken
The monoclonal antibody of NS1 protein was applied to develop the immunohistochemistry method(SABC method) in order to detect the NS1 protein.The study on the distribution of NS1 protein was detected in the different organs of chicken infected with HPAIV after 30-31hours.The main organs which can detect the positive signal of NS1 protein was the heart、pancreas、kidney and cerebellum granular layer.The positive signals were stronger than the others.The positive cells were involved in small or microvascular endotheliocyte、myocardial cell、renal tubular epithelial cell、glandular epithelium and epithelium.The results illustrated that the heart、pancreas、kidney cerebellum and microvascular endotheliocyte may be the main target organs in which HPAIV can duplicated effectively and product many effective virion.In this present study,It was presumed that the cardiovascular system was important for the duplication and diffusion of AIV.At the same time,the obvious associativity between the NS1 protein and apotosis was proved.
4.Screening and identification of host protein interacted with NS1 protein using the yeast two hybrid system
In present study,spleen cDNA library of chicken incubated with HPAIV(H5N1 subtype) was firstly constructed using the switching mechanism at 5′end of RNA transcript technology.Four proteins which can interact with NS1 protein were screened from this cDNA library using the yeast two hybrid system(Y2H).These proteins included the chicken interferon-stimulated gene12-2(ISG12-2),interferon regulatory factor 2(IRF2),Protein phosphatase 1F(PPM1F) and M protein of AIV.The interaction between NS1 protein and ISG12-2 and IRF2 was identified,both in vitro and in vivo,by bacteria two-hybrid system and GST fusion proteins sedimentation technology, respectively.It was deduced that some signal pathway associated with IFN expression may be inhibited by the protein-protein interaction,which would affect the expression of IFN and degress the IFN-mediated antiviral responses.The results would explain the function of NS1 protein and how to regulate the pathogenicity.These studies also will give some reference to the mechanism which HPAIV infects human being.
5.Identification of the interaction between NS1 protein and ISG12-2 or IRF2 using the bacterial two hybrid system and GST pull-down test
In this study,the interactons between NS1 protein with ISG12-2 and IRF2 protein were further identified using the bacterial two hybrid system and GST pull-down test,respectively.The results showed that NS1 protein interacted with ISG12-2 and IRF2 protein in vivo and in vitro.It was presumed that some pathways associated with the expressing of interferon were blocked and the expressing of interferon was inhibited by the interactions,which degraded the antivirus immune response and was beneficial for the duplication and diffusion of AIV.
引文
1.毕英佐.H9N2亚型禽流感的流行现状和防治措施.中国家禽,2007,3-5
2.曹梅,田夫林,庄文忠.禽流感病毒血凝素分子生物学研究进展.动物医学进展,2004,25(2):35-37
3.曹永浩,张仕坚,周元聪.干扰素调节因子家族和免疫调控.生命的化学,2006,26(5):387-389
4.陈伯伦,张泽纪,陈伟斌.禽流感研究Ⅰ:鸡A型禽流感病毒的分离与血清学初步鉴定.中国兽医杂志,1994,22(10):3-5
5.陈宣烁,钟婉玲,郑小敏,张佩娟.禽流感病毒分子生物学的研究进展.中国畜牧兽医,2006,(33)1:63-67
6.程从升,李希妍,王琦,赵新生,黄晶晶,聂凯,张晓光,蓝雨,柳燕,张智清,舒跃龙,姚立红,温乐英,王大燕,王伟.H5N1亚型禽流感病毒安徽株NS1基因的克隆及在原核系统的表达.微生物学报,2007,47(3):418-422
7.褚小刚,杨占秋,龚作炯.新型抗病毒因子APOBEC3G研究进展.中国艾滋病性病,2006,12(6):577-579
8.邓扬,刘殿峰,王坤,张锐.禽流感病毒NS1A蛋白诱导人肺癌细胞SPC2A1的凋亡.中国生物制品学杂志,2007,20(11):821-824
9.甘孟侯.禽流感(第2版).北京:中国农业出版社,2002,30-79
10.关薇,王建,贺福初.大规模蛋白质相互作用研究方法进展.生命科学,2006,18(5):507-512
11.郭霄峰,廖明,辛朝安.H9N2亚型禽流感病毒的致病特性研究.华南农业大学学报,2001,22(7):70-72
12.郭元吉,李建国,程小雯,王敏,邹毅,李钏华,蔡访潺,瘳华乐,张烨,郭俊峰,黄瑞敏,贝东.禽H9N2亚型流感病毒能感染人的发现.中国实验和临床病毒学杂志,1999,13(2):105-108
13.郭元吉,温乐英,王敏,李梓,张烨,郭俊峰.我国猪群中H9N2亚型毒株HA 和NA基因特性的研究.中华实验和临床病毒学杂志,2004,18(1):7-11
14.郭元吉,温乐英,张烨,王敏,郭俊峰,李梓,舒跃龙.猪在禽H9N2亚型流感病毒感染人中的作用.中华实验和临床病毒学杂志,2005,19(2):106-109
15.郭志儒.荷兰暴发高致病性禽流感并出现人感染.中国兽医学报,2003,23(3):257
16.胡国斌,刘怡,邹群.流感病毒诱导宿主细胞凋亡的形态学观察.湖北工学院学报,2000,15(3):56-57
17.黄淑坚,廖明,辛朝安,苏广基.A Ⅳ致病分子基础的研究进展.动物医学进展,2004,25(3):1-3
18.贾因棠,魏来,蒋栋,丛旭,费然.干扰素刺激基因ISG20真核表达载体的构建及其抗丙型肝炎病毒复制作用的研究.中国免疫学杂志,2006,22(11):997-1001
19.蒋芳.浅谈我国禽流感疫情对家禽业的影响及建议.中国畜牧杂志,2006,42(10):25-26
20.蒋露芳,姜庆五.甲型流感病毒宿主特异性研究进展疾病控制杂志.2005,9(1):49-52
21.金伯泉.固有免疫中模式识别受体及其信号转导当代免疫学中最伟大的发现之一.细胞与分子免疫学杂志,2006,22(1):1-3
22.金梅花.H5N1亚型禽流感病毒感染雏鸡免疫器官免疫变化及机理.[硕士学位论文].沈阳:东北农业大学,2007
23.李建丽,张万坡,毕丁仁.A型流感病毒NS1蛋白研究进展.微生物学报,2007,47(4):729-733
24.李建伟.欧亚大陆H9N2亚型禽流感病毒分子演化的研究.[博士学位论文].哈尔滨:东北农业大学,2002
25.李玲.细胞凋亡的分子机制及其调控因子.国外医学免疫学分册,2002,25(6):317-320
26.李先茜,杜培革,傅桂莲,董婕,齐立.应用定点突变技术进行流感病毒NS1蛋白功能的研究.北华大学学报,2004,5(4):316-320
27.李向忠,方芳,陈则.流感病毒神经氨酸酶不同区域的作用.生命科学研究,2005,9(2):55-61
28.李新梅,陈汉春.干扰素调节因子家族.生命科学研究,2002,6(1):8-12
29.林祥梅.鸭源流感病毒人工感染鸡的病理学研究.[硕士学位论文].南京:南京农业大学,1998
30.刘光伟,夏雪培,赵勇.Toll样受体信号传导途径的研究进展.动物学杂志,2005,40(6):117-121
31.刘金华,史为民,吴清民,郭玉璞.我国部分鸡源H9N2亚型流感病毒NS1基因序列分析.微生物学报,2003,43(5):547-553
32.刘晓静,孙坚.流感病毒诱导细胞凋亡及抗流感药物的研究进展.实用临床医学,2007,8(1):136-138
33.刘秀梵.家养水禽在A型流感病毒和新城疫病毒进化和疾病流行中的作用.中国家禽,2007,29(15):1-7
34.龙进学,王曲直,刘秀梵.禽流感病毒NS第263～277位核苷酸缺失降低其抗干扰素能力.微生物学通报,2006,33(2):34-39
35.卢建红,邵卫星,龙进学,刘秀梵.A型流感病毒毒力因子研究进展.动物医学进展,2004,25(4):63-66
36.陆承平.高致病性禽流感与流感病毒.中国病毒学,2004,19(2):204-207
37.罗玲,胡薛英,程国富,谷长勤,周全,李自力,赵雅心,周诗其,毕丁仁.H9N2亚型禽流感病毒人工感染蛋鸡的组织病理学研究.中国预防兽医学报,2004,26(4):259-261
38.罗以勤,王梁华,马玲,孔建新,焦炳华.细菌双杂交系统筛选与tumstatin45-132相互作用蛋白质.中华微生物与免疫学杂志,2007,27(2):101-106
39.马春全,赵德明,黄兴国,黄淑坚,卢玉葵.鹅高致病性禽流感病理组织学观察.中国预防兽医学,2006,28(2):175-177
40.彭开松,佘锐萍.动物病毒与宿主细胞的细胞凋亡.中国兽医杂志,2004,40(11):42-44
41.冉旭华,崔玉东,朴范泽.病毒感染与细胞凋亡.动物医学进展,2003,24(4):22-25
42.任仙文,李北平,王月兰,岳俊杰,梁龙.蛋白质相互作用的生物信息学研究进展.生物技术通讯,2006,17(6):976-980
43.萨姆布鲁克,拉塞尔.分子克隆实验指南(第三版).(黄培堂等 译).北京:科学出版社,2002,1481-1486
44.宋卉.雏鸵鸟免疫器官的形态学特点及鸡源NDV对雏鸵鸟致病机理的研究.[博士学位论文].武汉:华中农业大学,2007
45.孙博兴.H9N2亚型禽流感非结构蛋白NS1A基因的克隆表达及其诱导Hela细胞凋亡的研究.[博士学位论文].长春:吉林大学,2005
46.孙进华,吴明福,邢明伟,靳淼,王君伟.A型流感病毒非结构蛋白的功能及临床应用.生物化学与生物物理进展,2006,33(8):724-729
47.孙颖杰.禽流感研究进展.国外兽医学—畜禽传染病,1998,18(1):19-22
48.唐秀英,于康震,田国斌,赵传删.中国禽流感流行株的分离鉴定.中国畜禽传染病,1998,20(1):1-5
49.万春和,刘明.A型流感病毒M2蛋白研究进展.动物医学进展,2007,28(7):56-60
50.王艾琳,李坚.病毒与细胞凋亡.自然杂志,2004,26(3):125-128
51.王海波,安学丽,张艳贞,王爱丽,李巧云,晏月明.蛋白质相互作用研究方法及其应用.生物技术通报,2006(suppl):167-170
52.王海坤,韩代书.Toll样受体(TLRs)的信号转导与免疫调节.生物化学与生物物理进展,2006,33(9):820-827
53.王坤.禽流感病毒NS1A重组蛋白联合黄芩苷抗肿瘤作用研究.[博士学位论文].长春:吉林大学,2007
54.王忠田.1999-2000意大利禽流感的回顾.动物医学进展,2003,23(2):75
55.吴波,周晓军.细胞凋亡检测技术进展及其应用.临床实验病理学杂志,1997,8(3):262-264
56.吴志豪,王建,贺福初.大规模酵母双杂交技术研究蛋白质相互作用的应用.遗传,2006,28(12):1627-1632
57.谢月萍,刘鑫,叶进,江军,侯晓华.抗病毒分子APOBEC3G的研究进展.中西医结合肝病杂志,2007,17(4):255-257
58.淹泽刚.流感病毒感染与细胞凋亡.日本医学介绍,2004,25(9):411-412
59.杨齐衡,李林.酵母双杂交技术及其在蛋白质组研究中的应用.生物化学与生物物理学报,1999,31(3):221-225
60.杨涛,杜绍范,刘明.A型流感病毒NS1蛋白研究进展.现代畜牧兽医,2005,3:43-45
61.杨玉荣,佘锐萍,梁宏德.Toll-NF-kB信号途径及其介导的功能.细胞生物学杂志,2007,29:483-486
62.叶慧燕,熊思东.RIG-I介导的TLR非依赖性模式识别.生命的化学,2007,27(4):302-304
63.尹彦涛,夏平安,崔保安,赵云航,王建举,党占国,柴春霞.MxA抗病毒蛋白的研究概况.中国畜牧兽医,2008,35(1):87-89
64.于康震,崔尚金,付朝阳,唐秀英.禽流感与养禽业发展和人类健康.中国预防兽医学报,2000,22(4):313-315
65.于康震,付朝阳,崔尚金,步志高,唐秀英.我国禽流感防制研究进展.中国兽医学报,2001,21(1):103-106
66.余丹丹.两株H5N1亚型禽流感病毒诱导的细胞凋亡研究.[硕士学位论文].南京:南京农业大学,2005
67.张春斌,宋汉君,刘东璞.细胞凋亡与病毒感染.黑龙江医药科学,2004,27(6):63-64
68.张衡,李康生.流感病毒与细胞凋亡.微生物学免疫学进展,2007,35(2):76-78
69.张瑞莉,葛铭,张草,郑世民.鹅源H5N1亚型禽流感病毒感染雏鸡免疫器官的病理学观察.中国兽医科学,2007,37(4):333-337
70.张万坡.禽流感病毒感染鸡的抗原定位及基因差异表达研究.[博士学位论文].武汉:华中农业大学,2006
71.张泽纪,陈伯伦.禽流感研究Ⅱ:禽流感的发生情况和血清学调查.中国兽医杂志,1994,20(10):6-7
72.张志珍,段炼,李康生.华南流感病毒NS1基因特性研究.生物化学与生物物理进展,2004,31(3):237-243
73.张卓.H5N1亚型禽流感病毒感染雏鸡的病理学变化及其发生机制.[硕士学位论文].沈阳:东北农业大学,2007
74.赵明才,唐恩洁,朱道银.与细胞凋亡相关的细胞凋亡分子.国外医学病学分册,2000,8(1):25-29
75.赵仁亮.细胞凋亡的检测方法.医学综述,2002,8(3):130-131
76.郑丽舒,段招军.A型流感病毒M2蛋白疫苗的研究进展.病毒学报,2006,22(6):487-491
77.周晓娜.RIG-I信号转导途径在机体抗病毒中的作用.生命的化学,2007,27(5):381-383
78.朱建国.A型流感病毒基质蛋白研究进展.动物医学进展,2004,25(2):24-26
79.Akira S,Takeda K.Toll-like receptor signaling.Nat Rev Immunol,2004,4(7):499-511
80.Aleksandr S,Lipatov,Andreansky S,Webb y R J,Huls e DJ,Rehg J E,KraussS,Perez1 D R,Doherty P C,Webster R G,Sangster MY.Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice:the role of cytokines and B- and T-cell responses.J Gen Virol,2005,86(4):1121-1301
81.Alexander D J,Senne D A.Avian influenza in the Western Hemisphere including the Pacific Island and Australia.Avian Dis,2003,47:789-805
82.Alexander D J.A review of avian influenza in different bird species.Proceedings of the ESVV Symposium on animal influenza viruses,Gent.1999,Vet Microbiol,2000,74:3-13
83.Amonsin A,Payungpom S,Theamboonlers A.Genetic characterization of H5N1influenza A viruses isolated from zoo tigers in Thailand.Virology,2006,344(2):480-491
84.Aragon T,Luna Susana de la,Novoa,CarrascoL,Ortin J,Nietol A.Eukaryotic translation initiation factor 4GI Is a cellular target for NS1 Protein:a translational activator of influenza virus.Mol Cel Biol,2000,20(17):6259-6268
85.Avalos,Yu Z,Nayak D P.Association of influenza virus NP and M1 proteins with cellular cytoskeletal elements in influenza virus infected cells.Virology,1997,71:2947-2958
86.Baigent S J,Mccauley J W.Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture.Virus Res,2001,79(1-2):177-185
87.Banet-Noach C,Panshin A,Golender N,Simanov L,Rozenblut E,Pokamunski S,Pirak M,Tendler Y,Garcia M,Gelman B,Pasternak R,Perk S.Genetic analysis of nonstructural gene(NS1 and NS2) of H9N2 and H5N1 viruses recently isolated in Israel.Virus Gen,2007,34(2):157-168
88. Banks J,Speidel E S, Moore E, Plowright L, Piccirillo A,Capua I,Cordioli P,Fioretti A,Alexander D J.Changes in the haemagglutinin and the neuraminidase genes prior to the emergence of highly pathogenic H7N1 avian influenza viruses in Italy. Arch Virol, 2001, 146 (5): 963-973
89. Basler C F,Reid A H, Dybing J K, Janczewski T A, Fanning T G, Zheng H, Salvatore M,Perdue M L,Swayne D E,Garcia-Sastre A. Palese P, Taubenberger J K.Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes.PNAS, 2001,98 (5):2746-2751
90. Bass B L, Nishikura K, Keller W,Seeburg P H, Emeson R B, O'Connell M A, Samuel C E, Herbert H. A standardized nomenclature for adenosine deaminases that act in RNA.RNA, 1997, 3: 947-949
91. Bergmann M, Garcia-SastreA, Carnero E, Pehamberger H, Wolff K, Palese P, Muster T. Influenza Virus NS1 protein counteracts PKR-mediated inhibition of replication. J Virol, 2003, 74 (13): 6203-6206
92. Bornholdt Z A, Prasad B V.X-ray structure of influenza virus NS 1 effector domain. Nat Struct Mol Biol, 2006,13(6):559-560
93. Bridges C B, Lim W, Hu-Primmer J, Sims L,Fukuda K,Mak K H,Rowe T, Thompson W W,Conn L,Lu X,Cox N J,Katz J M.Risk of influenza A (H5N1) infection among poultry workers, Hong Kong ,1997-1998. J Infect Dis, 2002,185 (8) :1005-1010
94. Brown EG.Influenza Virus genetics.Biomed & Pharmacother 2000,54:196 -209
95. Browne E P, Wing B,Coleman D,Shenk T. Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: viral block to the accumulation of antiviral mRNAs. J Virol, 2001, 75: 12319-12330
96. Brydon E W A,Smith H,Sweet C. Influenza A virus induced apoptosis in bronchiolar epithelial (NCI2H292) cells limits pro-inflammatory cytokine release. J Gen Virol 2003,84: 2389-2400
97. Burgui I, Aragon T, Ortin J, Nieto A.PABP1 and eIF4GI associate with influenza virus NS1 protein in viral mRNA translation initiation complexes. J Gen Virol, 2003, 84:3263-3274
98. Cameron K R, Gregory V, Banks J, Brown I H, Alexander D J, Hay A J,LinY P. H9N2 subtype influenza A viruses in poultry in Pakistan are closely related to the H9N2 viruses responsible for human infection in Hong Kong. Virology,2000,278:36-41
99. Castrucci M R, Kawaoka Y.Biologic importance of neuraminidase stalk length in influenza A virus. J Virol, 1993,67 (2): 759-764
100. Causier B,Davies B. Analysing protein-protein interactions with the yeast two-hybrid system. Plant Mol Biol, 2002,50(6): 855-870
101. Chanturiya A N, Basanez G,Schubert U, Nenklein P,Yewdell J W,Zimmerberg J.PB1-F2,an influenza A virus-encoded proapoptotic mitochondrial protein, creats variably sized pores in planar lipid membranes. J Virol, 2004, 78(12):6304-6312
102.Chen H, Bright R A, Subbarao K,Smith C, Cox N J, Katz J M, Matsuoka Y.Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Res, 2007, 128: 159-163
103.Chen J, Lee KH, Steinhauer D A, Stevens D J, Skehel J J,Wiley D C. Structure of the haemagglutinin precursor cleavage site.a determinant of influenza pathogenicity and the origin of the labile conformation.Cell, 1998,95: 409-417
104.Chen W, Calvo P A, Malide D, Gibbs J, Schuber U, Bacik I, Basta S, O'Neill R, Schickli J, PaleseP, Henklein P, Bennink J R, Yewdell J W. A novel influenza A virus mitochondrial protein that induces cell death. Nat Medicine, 2001, 7 (12): 1306-1312
105.Chen Z, Li Y, Krug R M. Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 39-end processing machinery. EMBO J,1999,18(8): 2273-2283
106.Chien CY, XuY, Xiao R,Aramini J M, Sahasrabudhe PV, Krug R M, MontelioneG T. Biophysical characterization of the complex between double-stranded RNA and the N-terminal domain of the NS1 protein from influenza A virus: evidence for a novel RNA-binding mode. Biochemistry, 2004,43(7): 1950-1962
107.Choi Y K, Ozaki H, Webby R J,Webster R G, Peiris J S ,Poon L, Butt C,Leung Y H, Guan Y.Continuing evolution of H9N2 influenza viruses in South eastern China. Virology, 2004, 78 (16) :8609-8614
108.Colamussi M L, White M R,Crouch E,Hartshonn K L. Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria. Blood, 1999,93 (7):2395-2403
109.Czabotar P E,Martin S R, Hay A J.Studies of structural changes in t he M2 proton channel of influenza A virus by tryptophan fluorescence. Virus Res,2004,99 (1) :57261
110.De L S,Bartolome J,Carreno V.Hepatitisc virus core protein down-regulates transcription of interferon-induced anti-ral genes.J Infect Dis,2005,191 (1) :93-99
111. Der S D,Zhou A, Williams B R G, Silverman H. Identification of genes differentially regulated by interferon α, β or γ using oligonucleotide arrays.PNAS USA, 1998,95, 15623-15628
112.Dundon W G,Milani A,Cattoli G,Capua I.Progressive truncation of the Non-Structural 1 gene of H7N1 avian influenza viruses following extensive circulation in poultry, Virus Res, 2006, 119(2): 171-176
113.Duong-Ly K C, Nanda V, Degrado W, Howard K P. The conformation of the pore region of t he M2 proton channel dependson lipid bilayer environment. Protein Sci, 2005,14(4):856-861
114.Ehrhardt C, Wolff T, Pleschka S, PlanzO, Beermann W, Bode J G, Schmolke M, LudwigS.The influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses. J Virol,2007,81(7):3058-3067
115.Ellis A E. Innate host defense mechanisms of fish against viruses and bacteria. Dev Comp Immunol, 2001,25: 827-839
116. Ellis T M, Bousfield B, Bissett L, Dyrting K, Luk G S M, Tsim S T, Sturm-Ramirez K, Webster R G, Guan Y, Peiris M J S.Investigation of outbreaks of highly pathogenic H5N1 avian influenza in waterfowl and wild birds in Hong Kong in late 2002, Avian Pathol, 2003, 33:492-505
117.Enami K, Sato T A, Nakada S. Influenza virus NS1 protein stimulates translation of the M1 protein, J Virol, 1994,68: 1432-1437
118.Enami M, Enami K. Characterization of Influenza virus NS1 protein by using a novel helper-virus-free reverses genetic system. J Virol,2000,74(12): 5556-5561
119.Esnault C, Millet J, Schwartz O, HeidmannT.Dual inhibitory effects of APBOEC family proteins on retrotransposition of mammalian endogenous retroviruses. Nucleic Aacids Res, 2006,34 (5): 1522-1531
120.Espert L, Degols G,Gongora C, Blondel D,Williams B R, Silverman R H,Mechti N. ISG20, a new interferon induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses. J Biological Chemistry, 2003, 278 (18): 16151-16158
121.Fagerstam LG,Frostell-Karlsson A, Karlsson R, Persson B,Ronnberg I. Biospecific interaction analysis using SPR detection applied to kinetic, binding site and concentration analysis. J Chromatogr, 1992,597: 397- 410
122.Falcon A M, Fortes P, Marion R M, Beloso A, Ortin J. Interaction of influenza virus NS1 protein and the human homologue of Staufen in vivo and in vitro. Nucleic Acids Res,1999,27(11):2241-2247
123.Falcon A M, Marion R M, Zurcher T, Gomez P, Portela A, Nieto A, Ortinl J.Defective RNA replication and late gene expression in temperature-sensitive Influenza viruses expressing deleted forms of the NS1 protein J Virol, 2004,78(8):3880-3888
124.Femandez-SesmaA, Marukian S, Ebersole B J, Kaminski D, Park M S, Yuen T, Sealfon S CGarcfa-Sastre A ,Moran T M. Influenza Virus Evades Innate and Adaptive Immunity via the NS1 Protein. J Virol, 2006,80(13): 6295-6304
125.Fields S, Song O K. A novel genetic system to detect protein-protein interactions. Nature, 1989,340(6230): 245-246
126.Fouchier R A, Munster V, Wallensten A,Bestebroer T M,Herfst S, Smith D, Rimmelzwaan G F, Olsen B, Osterhaus A D. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol, 2005 ,79 (5) :2814-2822
127.Gambaryan A S, Robertson J S, Matrosovich M N. Effects of egg-adaptation on the receptor-bingding properties of human influenza A and B viruses. Virology, 1999, 258 (2): 232-239
128.Gambaryan A S, Tuzikov A B, Piskarev V E.Specification of receptor-binding phenotypes of influenza virus isolates from different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and H3 influenza A and influenzaB viruses share a common high binding affinity for 6'-sialy (Nacetyllac-tosamine). Vi rology, 1997, 232 (2):345-350
129.Geiss G K,Salvatore M, Tumpey T M,Carter V S,Wang X,Basler C F,Taubenberger J K,Bumgarner R E, Palese P, Katze M G,Garcia-Sastre A. Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza.PNAS, 2002,99(16): 10736-10741
130. George C X and Samuel C E.Human RNA specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon-inducible. PNAS USA, 1999,96: 4621-4626
131.Gjermandsen I M, Justesen J, Martensen P M.The interferon-induced gene isg12 is regulated by various cytokines as the gene 6-16 in human cell lines. Cytokine, 2000,12(3): 233-238
132.Gong J,Xu W,Zhang J.Structure and functions of influenza virus neuraminidase. Curr Med Chem,2001 , 14 (1): 113-122
133.Goto H, Kawaoka Y. A novel mechanism for the acquisition of virulence by a human influenza A virus. PNAS USA, 1998, 95: 10224-10228
134.Gougeon M L, Motagnier L. Apoptosis in AIDS. Science, 2002,260:1269-1272
135.Guan.Y,Shortridge K F,Krauss S,Webster R G. Molecular characterization of H9N2 influenza viruses: were they the donors of the"internal"genes of H5N1 viruses in Hong Kong? PNAS USA, 1999, 96(16):9363-9367
136.Gubareva LV, Kaiser L, Hayden FG.Influenza virus neuraminidase inhibitors. Lancet ,2000,355 (9206) :827-835
137.Guo Y J,Krauss S, Senne D A,Senne D A, Mo I P,Lo K S. Characterization of the pathogenicity of the member of the newly established H9N2 influenza virus lineages in avian.Virology,2000, 269(1):278-288
138.Hacker H, Redecke V, Blagoev B, Kratchmaroval, Hsu L C, Wang G G, KampsEyal Raz M P, WagnerH, Hacker G, Mann M , Karin M. Specificity in Toll-like receptor signalling through distinct effector functions of T RAF3 and TRAF6, Nature, 2006, 439 (7073): 204-207
139.Hale B G, JacksonD, Chen Y H, Lamb RA, Randall R E. Influenza A virus NS1 protein binds p85β and activates phosphatidylinositol-3-kinase signaling. PNAS USA, 2006, 103: 14194-14199
140.Haller O, Kochs G. Interferon-induced Mx proteins: dynamin-like GTPases with antiviral activity. Traffic,2002,3(10):710-714
141.Harada H, Takahashi E I.Structure and regulation of the human interferon regulatory factor 1 and IRF 2 genes; implication for a gene network in the interferon system. Mol Cell Biol, 1994, 14(2): 1500-1509
142.Harvey B P,Banga S S, Ozer H L, Regulation of the multifunctional Ca2+/ calmodulin-dependent protein kinase II by the PP2C phosphatase PPM1F in fibroblasts. J Biol Chem,2004, 279 (23): 24889-24898
143.Hatta M, GaoP, Halfmann P, Kawaoka Y.Molecular basis for high virulence of Hong Kong H5N1 influenza A vieuses. Science,2001, 293: 184021842
144.Hayman A,Comely S,Lackenby A,Hartgroves L CGoodbourn S,McCauley J W,Barclay W S. NS1 protein of avian Influenza A virus can act as antagonist of the human alpha/beta interferon response. J Virol, 2007, 81(5):2318-2327
145.Hechtfischer A, Marschall M, Helten A, Boswald C, Meier-Ewert H. A highly cytopathogenic influenza C virus variant induces apop tosis in cell culture. J Gen Virol ,1997,78: 1327-1330
146.Heim M H. RIG-I: an essential regulator of virus-induced interferon production.J Hepatol,2005, 42:431-433
147.Hinshaw V S, Olsen C W, Sissoko N D , Evans D. Apoptosis: a mechanism of cell killing by influenza A and B viruses .J Virol, 1994,68: 3667-3673
148.Homme P J, Easterday B C.Avian influenza virus infection. I.Charaterization of an influenza A/Turkey/Wisconsim/1966 virus, Avian Dis, 1970, 14:66-74
149.Horimoto T, Kawaoka Y. Reverse genetics provides direct evidence for a correlation of hemagglutinin cleavability and virulence of an avian influenza A virus. J Virol, 1994,68 (5): 3120-3128
150.Horimoto T,Kawaoka Y. Pandemic threat posed by avian influenza A viruses.Clin Microbiol Rev, 2001, 14(1): 129-149
151.Horio T, Murai M, Inoue T, Hamasaki T, Tanaka T, Ohgi T.Crystal structure of human ISG20, an interferon induced antiviral ribonuclease. FEBS Letters, 2004,577 (122): 111-116
152.Hornickova Z.Different progress of MDCK cell death after infection by two different influenza virus isolates. Cell Biochem Funct, 1997,15: 87-93
153.Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H,Poeck H,Akira S,Conzelmann K K,Schlee M,Endres S,Hartmann,G.5-prime-triphosphate RNA is the ligand for RIG-I. Science , 2006,314:994-997
154.Hoshino K, KaishoT, Iwabel T, Takeuchil O , Akira S. Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation. Int Immunol, 2002,14(10): 1225-1231
155.Hu J C, Kornacker, Cx M, Hochschild A. Escherichia coli one- and two-hybrid systems for the analysis and identification of protein-protein interactions. Methods, 2000,20(1): 80-94
156.Huang Q, Liu D, Majewski P, Schulte L C, Korn J M Young, R A, Lander E S, HacohenN.The plasticity of dendritic cell responses to pathogens and their components. Science, 2001, 294 (5543): 870875
157.Huh W K, Falvo J V,Gerke L C, Carroll A S,Howson R W,Weissman J S, O'Shea E K.Global analysis of protein localization in budding yeast. Nature, 2003,425(6959): 686-691
158.Ito T, Kobayashi Y,Morita T,Horimoto T, Kawaoka Y. Virulent influenza A Viruses induce apoptosis in chickens. Virus Res, 2002,84:27-35
159.Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol, 2004, 5 (10): 987-995
160.Jackson D, Hossain M J, Hickman D, Perez D R, Lamb R A. A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity. PNAS USA, 2008,105(11):4381-4386
161.Jeffrey I W,Bushell M, Tilleray V J,Morley S, Clemens M J. Inhibition of protein synthesis in apoptosis: differential requirements by the tumor necrosis factor a and a DNA-damaging agent for Caspases and the double-stranded RNA-dependent protein kinase.Cancerr Res, 2002, 62: 2272-2280
162.Kaisho T, Akira S. Toll-like receptor function and signaling. J Allergy Clin Immunol, 2006,117 (5): 979-987
163.Kamille C J,Smidt, HansenL L, Sogaard T M, Petersen L K, Knudsen U B, Martensen P M. A nine-nucleotide deletion and splice variation in the coding region of the interferon induced ISG12 gene. Biochimica et Biophysica Acta,2003,1638: 227- 234
164.Kasper H, Janssen E M, Kim S O, Alexopoulou L, Flavell R A, Han J, Beutler B. Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nat Immunol, 2003,4 (12): 1223 -1229
165.Kass, Arkin T. How pH opens a H~+ channel: the gating mechanism of influenza A M2 .St ructure, 2005 ,13 (12): 1789-1798
166.Kawaoka Y, Naeve C W, Webster R G. Is virulence of H5N 2 influenza viruses in chickens associated with loss of carbohydrate from the hemagglutinin? Virology, 1984,139 (2): 303-316
167.Keawcharoen J, Oraveerakul K, Kuiken T,Fouchier R A,Amonsin A.Payungporn S.Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis, 2004, 10: 2189-91
168.Khatchikian D, Orlich M, Rott R. Increased viral pathogenicity after insertion of a 28S ribosomal RNA sequence into the haemagglutinin gene of an influenza virus. Nature, 1989,340: 156-157
169.Kiyoko I H, Taisuke H, Yutaka F, Yoshihiro K. Generation of influenza A virus NS2 (NEP) mutants with an altered nuclear export signal sequence. J Virol, 2004,78 (18): 10149-10155
170.Klenk H D, Ohuchi M, OhuchiR, Konig G, Angliker H, Shaw E, Stieneke-Grober A, Vey M, Garten W.Proteolytic activation as a determinant for the pathogenicity of influenza viruses: substractes and proteases,Proc 3rd Int Symp A vian Influenza.Madison: University of Wisconsin Press, 1992:182-198
171.Knapp S, Yeel J, Frodshama J, Hennig B J W, Hellier S, Zhang L, Wright M, Chiaramonte M, Graves M, Thomas H C,Hill AVS, Thursz M R. Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection : roles of MxA, OAS and PKR.Genes Immun,2003 ,4(6) :411-419
172.Koh C G, Tan E J, Manser E, Lim L. The p21 -activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family. Curr Biol ,2002,12 (4): 317-321
173.Krug R M, Yuan W, Noah D L, Latham A G. Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein. Virology,2003,309(2): 181 -189
174.Kuiken T, Rimmelzwaan G, van Riel D,van Amerongen G, Baars M, Fouchier R. Avian H5N1 influenza in cats. Science, 2004,306: 241
175.Labrada L, LiangX H, Zheng W, JohnstonC, LevineB. Age-Dependent Resistance to Lethal Alphavirus Encephalitis in Mice: Analysis of Gene Expression in the Central Nervous System and Identification of a Novel Interferon-Inducible Protective Gene, Mouse ISG12. J Virol,2002,76(22): 11688-11703
176.Lamb R A, Choppin P W. Segment 8 of the influenza virus genome is unique in coding for two polypeptides. PNAS USA ,1979,76:4908-4912
177.Lemaitre B.The road to Toll. Nat Rev Immunol, 2004,4 (7): 521-527
178.U C, Yu K,Tian G,Yu D,Liu L, Jing B, Ping J, Chen H . Evolution of H9N2 influenza viruses from domestic poultry in Mainland China. Virology,2005,340 (1):70-83
179.Li K S, Xu K M, Peiris J S M, Poon L L M, Yu K Z, Yuen K Y, Shortridge K F, Webster R G, Guan Y.Characterization of H9 Subtype Influenza Viruses from the Duck of Southern China :a Candidate for the Next Influenza Pandemic in Humans? J Virol ,2003,77:6988-6994
180.Li X D, Sun L, Seth R B, Pineda G, Chen Z J.Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. PNAS USA ,2005,102:17717-17722
181.Li Y, Chen Z Y, Wang W, Bake r C C, Kru g R M. The 3'-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo.RNA,2001, 7(6): 920-931
182.Li Z, Jiang Y, Jiao P, Wang A, Zhao F, TianG, Wang X, Yu K, Bu Z, ChenH.The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J Virol, 2006,80(22): 11115-11123
183.Liew F Y, Xu D,Brint E K, O'Neill L A.Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immuno, 2005, 5(6): 446-458
184.Lin C B, Zimmer S G, Lu Z J, Holland R E, Dong Q, Chambers T M. The involvement of a stress activated pathway in equine influenza virus-mediated apoptosis. Virology,2001,287: 202-213
185 .Lin Y P, Shaw M, Gregory V,Cameron K, Lim W, Klimov A, Subbarao K, Guan Y, Krauss S,Shortridge K, Webster R, Cox N,Hay A. Avian-to-human transmission of H9N2 influenza A viruses: relationship between H9N2 and H5N1 human isolate, PNAS USA , 2000, 97(17):9654-9658
186.Lipatov A S, Andreansky S, Webby R J, Hulse D J, Rehg J E, Krauss S, Perezl D R, Doherty P C, Webster R G , Sangster M Y.Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol, 2005, 86 (4): 1121-11301
187.Liu J H, Okazaki K, Shi W M, Wu Q M, MweeneA S, Kida H. Phylogenetic analysis of neuraminidase gene of H9N2 influenza viruses prevalent in chickens in China during 1995-2002. Virus Gen, 2003,27(2): 197-202
188.Liu J, Lynch P A, Chien C Y, Montelione G T, Krug R M,Berman H M. Crystal structure of the unique multifunctional RNA binding domain of the influenza virus NS1 protein. Nat Struct Biol, 1997,4(11): 896-899
189.Liu T, Ye Z. Alteration of the basic amino acid domain of wild-type matrix protein reduced influenza virus rep lication at non-permissive temperature. Int Congr Ser, 2004, 1263: 83-89.
190.Lommer B S, Luo M. Sructural plasticity in Influenza virus protein NS2 (NEP). J Biol Chem, 2002,277 (9):7108-7117
191.Ludwig S, Schultz U, Mandler J, Fitch W M, Scholtissek C.Phylogenetic relationship of the nonstructural (NS) genes of influenza A viruses.Virology, 1991,183(2): 566-577
192.Ludwig S, Wang X, Ehrhardt C, Zheng H, Donelan N, Planz O, Pleschka S, Garcia-Sastre A, Heins G, WolffT.The influenza A virus NS1 protein inhibits activation of Jun N-Terminal kinase and AP-1 transcription factors. J Virol, 2002, 76: 11166-11171
193 .Marion R M, Zurcher T, Luna S de la, Ortin J. Influenza virus NS1 protein interacts with viral transcription-replication complexes in vivo. Gen Virol, 1997,78 :2447-2451
194.Martensen P M, Sogaard T M M, Gjermandsen I M, Buttensch0n H N, Rossing A B, Bonnevie-Nielsen V, Rosada C, Simonsen J L, Justesen J. The interferon alpha induced protein ISG12 is localized to the nuclear membrane.. Eur J Biochem, 2001, 268: 5947-5954
195.Matrosovich M,Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci M R, Donatelli I,Kawaoka Y. Early alterations of the receptor binding properties of H1, H2 and H3 avian influenza virus hemagglutinins after their introduction into mammals J Virol, 2000, 74 (18): 8502-8512
196.Matrosovich M,Zhou N, Kawaoka Y, Webster R. The surface glycoprotein of H5 Influenza viruses isolated from humans,chickens,and wild aquatic birds have distinguished properties J Virol, 1999,73 (2): 1146-1155
197.McCullers J A, Bartmess K C. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumonia.J Infect Dis, 2003 ,187(6): 1000-1009
198.Meylan E .Tschopp J.Toll-Like Receptors and RNA Helicases: Two parallel ways to triggerantiviral responses Molecular cell, 2006,22(5):561-569
199.Mibayashi M, Martinez-Sobrido L, Loo Y M, Cardenas W B, Gale MJr, Garcia-Sastre A. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus.J Virol, 2007,81: 514-524
200.Mikhail N, Krauss M S.H9N2 influenza A viruses f rom poultry in Asia have human virus-like receptor specificity. Virology,2001,281 (2): 156-162
201. Min J Y, Krug R M.The primary function of RNA binding by the influenza A virus NS1 protein in infected cells:Inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway. PNAS, 2006, 103(18):7100-7105
202.Min J Y, Li S, Sen G C.A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. Virology,2007,363:236-243
203.Mo I P, Brugh M, Fletcher O J.Rowland G N, Swayne D E.Comparative pathology of experimentally inoculated with avian influenza viruses of low and high pathogenicity. Avian Dis, 1997,41:125-1361
204.Mori I, Komatsu T, Takeuchi K, Nakakuki K, Sudo M, Kimura Y. In vivo induction of apoptosis by influenza virus. J Gen Virol, 1995,76(ptl 1):2869-2873
205.Mossman K L,Macgregor P F,Rozmus J J,Goryachev A B, Edwards A M, Smiley J R. Herpes simplex virus triggers and then disarms a host antiviral response. J Virol, 2001,75: 750-758
206.Nakajima K, Nobusawa E, Nakajima S. Volution of the NS genes of the influenza A viruses. Ⅱ. The genetic relatedness of the NS genes of animal influenza viruses. Virus Genes, 1990,4(1): 15-26
207. Nakajima K.The mechanism of antigenic shift and drift of human influenza virus. N ippon Rinsho,2003,61 (11): 1897-905
208.Navarro F, Bollman B, Chen H, Konig R,Yu Q, Chiles K,Landau NR.Complementary function of the two catalytic domains of APOBEC3G. Virology,2005,333 (2 ):374-386
209.Nemeroff M E, Barabino S M, Li Y,Keller W, Krug R M. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell/,1998,1(7):991-1000
210.Neumann G, Hughes M T, Kawaoka Y. Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1.EMBO J, 2000,19(24):6751-6758
211.Nguyen L H, Espert L,Mechti N,Wilson D M 3rd. The human interferon- andestrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro. Biochemistry, 2001, 40: 7174-7179
212.Nichols J E, Niles J A, Roberts N J J r.Human lymphocyte apoptosis after exposure to influenza A virus.7 Virol, 2001, 75(13): 5921-5929
213.Obenauer J C, Denson J, Mehta P K, Su X, Mukatira S, Finkelstein D B, XuX, Wang J, Ma J, Fan Y, Rakestraw K M, Webster RG, Hoffmann E, KraussS, Zheng J, Zhang Z, Naeve C W. Large-scale sequence analysis of avian influenza isolates.Science, 2006,311:1576-1580
214.Ohuchi M, Asaoka N, Sakai T.Roles of neuraminidase in the initial stage of influenza virus infection. Microbes Infect, 2006,8 (5): 1287-1293
215.O'Neill R E, Talon J, Palese P.The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J,1998,17,288-296
216.Opitz B, Rejaibi A, Dauber B, Eckhard J,Vinzing M, Schmeck B, Hippenstiel S, Suttorp N,Wolff T. IFN-β induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Cell Microbiol,2007, 9(4):930-938
217.Pasare C, Medzhitov R.Control of B-cell responses by Toll-like receptors. Nature,2005, 438 (7066): 364-368
218.Peiris M,Guan Y,Markwell D,Ghose P,Webster R C, Shortridge K F.Cocirculation of H9N2 and contemporary "human"influenza A viruses in pigs in southeastern China: Potential for genetic reassortment. J Virol,2001,75(20):9679-9686
219.Peiris M,Yam W C, Leung C W, Chan K H, Ip P L, Lai R W, Orr W K, Shortridge K F.Human infection with influenza H9N2. Lancet, 1999, 354:916-917
220.Perez D R, Lim W, Seiler J P, Yi G, Peiris M, Shortridge K F, Webster R G.Role of Quail in the interspecies transmission of H9 influenza A viruses: molecular changes on HA that correspond to adaptation from ducks to chickens.J Virol,2003, 77(5): 3148-3156
221.Pichlmair A,Schulz O,Tan C P,Naslund T LLiljestrom P, Weber F,Reise-Sousa C. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5-prime-phosphates. Science, 2006, 314:997-1001
222.Price G E, Smith H,Sweet C.Differential induction of cytotoxicity and apop tosis by influenza virus strains of differing virulence.J General Virol, 1997,78: 2821-2829
223.Qian X Y, Alonso-Caplen F, Krug R M. Two functional domains of the influenza virus NS1 protein are required for regulation of nuclear export of mRNA.J Virol, 1994, 68(4):2433 - 24411
224.Qiu Y, Krug RM. The influenza virus NS1 protein is a poly(A)-binding protein that inhibits nuclear export of mRNAs containing poly(A).J Virol, 1994,68(4): 2425-2432
225.Qiu Y, Nemeroff M,Krug RM.The influenza virus NS1 protein binds to a specific region in human U6 SnRNA and inhibits U6-U2 and U6-U4 SnRNA interactions during splicing.RNA ,1995,1(3):304-316
226.Quinlivan M, Zamarin D, Garcia-Sastre A. Attenuation of equine influenza viruses through truncations of the NS1 protein. Virology, 2005, 79 (13): 8431-8439
227.Reinhardt J, Wolff T. The influenza A virus M 1 protein interacts with the cellular receptor of activated C kinase (RACK) 1 and can be phosphorylated by protein kinase C. Vet Microbiol, 2000,74(1-2): 87-100
228.Rigaut G, ShevchenkoA, Rutz B, WilmM, MannlM, SeraphinB. A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol, 1999,17(10): 1030-1032
229.Rimmelzwaan G F, van Riel D, Baars M, Bestebroer T M, van Amerongen G, Fouchier R A. Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am J Pathol,2006, 168:176-83
230.Ronni T, Matikainen S, Sareneva T, Melen K, Pirhonen J, Keskinen P, Julkunen I. Regulation of IFN-α/β, MxA, 2-5-oligoadenylate synthetase and HLA gene expression in influenza A-infected human lung epithelial cells. J Immunol, 1997,158, 2363-2374
231.Saito T, Lim W, Suzuki T, Suzuki Y, Kida H, Nishimura S I, Tashiro M. Characterization of a human H9N2 influenza virus isolated in Hong Kong. Vaccine, 2001,209(1-2): 125-133
232.Schultz-Cherry S, Dybdahl-Sissoko N, Neumann G, Kawaoka Y, Hinshaw V S. Infuenza virus NS1 protein induces apoptosis in cultured cells. J Virol, 2001,75(17):7875-7881
233.Seo S H , Hoffmann E ,Webster RG. The NS1 gene of H5N1 influenza viruses circumvents the host antiviral cytokine responses. Virus Res,2004,103(122): 107-1131
234.Seo S H, Hoffmann E, Webster R G. Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med, 2002, 8(9):950-9541
235.Serebriiskii I G, Fang R, Latypova E, Hopkins R, Vinson C, Joung J K, Golemis E A. A combined Yeast/Bacteria two-hybrid system: development and evaluation. Mol Cell Proteomics, 2005, 4(6): 819-826
236.Seth R B, Sun L,Ea C K,Chen Z J. Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-kappaB and IRF3.Cell, 2005,122:669-82
237.Seth R B,Sun L, Chen Z J.Antiviral innate immunity pathway. Cell Res,2006, 16: 141-147
238.Sha B, Luo M.Structure of a bifunctional membrane RNA binding protein, influenza virus matrix protein Ml. Nat Struct Biol, 1991,4 (3): 239-244
239.Shin Y K, Li Y, Liu Q, Anderson D H, Babiuk L A, Zhou Y. The influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate anti-apoptotic signaling responses.J Virol,2007,81(7):3058-3067
240.Shin Y K, Liu Q, Tikoo S K, Babiuk L A, Zhou Y. Influenza A virus NS1 protein activates the Phosphatidylinositol 3-kinase (PI3K)/Akt pathway by direct interaction with the p85 subunit of PI3K. J Gen Virol, 2007, 88(Pt 1):13-18
241.Shinya K, Awakura T, Shimada A, Silvano F D, Umemura T, Otsuki K. Pathogenesis of pancreatic atrophies by avian influenza A virus infection .Avian Pathol, 1995, 24 :623-632
242.Shortridge K F, Zhou N N, Guan Y,Gao P, Ito T, Kawaoka Y,Kodihalli S, Krauss S, Markwell D, Murti KG, Norwood M, Senne D, Sims L, Takada A, Webster R G. Characterization of avian H5N1 influenza viruses from poultry in Hong Kong.Virology,1998,252:331-342
243.Shu Y, Yu H, Li D. Lethal Avian Influenza A (H5N1) infection in a pregnant woman in Anhui province China. New Engl J Med, 2006,354(13): 1421-1422
244.Sidhartha K, Biswas,Paul L. Influenza Virus Nucleoprotein Interacts with Influenza Virus Polymerase Proteins. Virology, 1998,8 :5493-5501
245.Smith E J, Marie I, Prakash A. IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or NF-kB kinase but is blocked by vaccinia virus E3L protein. J Biol Chem, 2001,276(12):8951-8957
246.Solorzano A,Webby R J, Lager K M, Janke B H,Garcia-Sastre A,Richt J A.Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. J Virol, 2005, 79 (12): 7535-7543
247.Songserm T, Amonsin A, Jam-on R, Sae-Heng N, Meemak N, Pariyothorn N.Avian influenza H5N1 in naturally infected domestic cat. Emerg Infect Dis,2006,12:681-683
248.Stark G R, Ken I M, Williams B R G, Silverman R H, Schreiber R D. How cells respond to interferons. Ann Rev Biochem, 1998, 67,227-264
249.Sturm-Ramirez K M, Hulse-Post D J, Govorkova E A, Humberd J, Seiler P, Puthavathana P, Buranathai C, Nguyen T D, Chaisingh A, Long H T, Naipospos T S P, Chen H, Ellis T M,Guan Y, Peiris J S M, Webster R G. Are Ducks Contributing to the endemicity of highly pathogenic H5N1 influenza virus in asia? J Virol, 2005 79(17): 11269-11279
250.Suarea D L, Perdue M L. Multiple alignment comparison of the non-structural genes of influenza A viruses. Virus Res, 1998, 54 (1):59-69
251.Suarez D L.Evolution of avian influenza viruses. Vet Micro, 2000, 74: 15-27
252.Sun Q,Sun L, Liu H H.Chen X, Seth R B, Forman J, Chen Z J. The specific and essential role of MAVS in antiviral innate immune responses. Immunity ,2006,24: 633-642
253.Suzuki T, Takahashi T, GuoC T, Jwa Hidari K I P, MiyamotoD, GotoH, Kawaoka Y, SuzukiY.Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication. J Virol ,2005,79(18) :11705-11715
254.SuzukiY, Ito T, Suzuki T, Miyamoto D, Hidari K I P J, Guo C T, Kida H, Webster G R , Chambers T M, Kawaoka Y.Sialyl sugar chains as receptors and determinants of host range of influenza A viruses. International Congress Serie,2001,1219 :521-525
255.Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K,Shibue T, Honda K, Taniguchi T. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature,2003,424: 5162-523
256.Takeda K, Kaisho T, Akira S.Toll-like receptors. Annu Rev Immunol, 2003,21: 335-376
257.Takizawa T, Matsukawa S,Higuchi Y,Nakamura S, Nakanishi Y,Fukuda R.Induction of Programmed cell Death (apoptosis) by Influenza Virus Infection in Tissue Culture Cells. Gen Virol, 993,74 :2347-2355
258.Tamanna A, Asad U K. Identification of a casein kinase II phosphorylation domain in NS1 protein of H5N1 influenza virus. Bioinformation, 2007, 2(2): 57-61
259.Tan KM ,Chan S L,Tan K O,Yu V C.The Caenorhabditis elegans sex-determining protein FEM-2 and its human homologue, hFEM-2, are Ca2+/calmodulin-dependent protein kinase phosphatases that promote apoptosis. J Bio Chem, 2001, 276 (47): 44193-202
260.Thanawongnuwech R,Amonsin A, Tantilertcharoen R, Damrongwatanapokin S, Theamboonlers A, Payungporn S. Probable tiger-to-tiger transmission of avian influenza H5N1. Emerg Infect Dis, 2005, 5:699-701
261. Thomas A V, Palm M, BroersA D, Zezafoun H, Desmecht DJM. Genomic structure, organization and promoter analysis of the bovine (Bostaurus) Mxl gene. Gene,2004,26 :67-75
262.TorisuH,Kusuhara K, KiraR, BassunyW M, Sakai Y,Sanefuji M, Takemoto M, Hara T. Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis, Neurology, 2004,62 (3) :457-460
263.Treanor J J, Snyder M H, London W T, Murphy B R.The B allele of the NS gene of avian influenza viruses, but not the A allele, attenuates a human influenza A virus for squirrel monkeys. Virology, 1989,171 (1): 1-9
264.Turpin E,Luke K, Jones J, Tumpe y T, Konan K, Schultz-Cherry S. Influenza virus infection increases p53 activity: role of p53 in cell death and viral replication.J Virol, 2005,79:8802-8811
265.Ungchusak K, Auewarakul P,Dowell S F, Kitphati R, Auwanit W, Puthavathana P, Uiprasertkul M, Boonnak K, Pittayawonganon C,Cox N J, Zaki S R, Thawatsupha P, Chittaganpitch M, Khontong R, Simmerman J M, Chunsutthiwat S. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med, 2005, 352(4) :333-340
266.Vattem, Krishna M, Staschke,Kirk A,Wek, Ronald C. Mechanism of activation of the double-stranded-RNA-dependent protein kinase,PKR. Eur J Biochem, 2001, 268: 3674-3684
267. Vey M, Orlich M, Adler S, Klenk H D, Rott R,Garten W. Hemagglutinin activation of pathogenic avian influenza viruses of serotype H7 requires the protease recognition motif R-X-K/R-R. Virology, 1992,188(1): 408-413
268.Vilcek J. Boosting p53 with interferon and viruses. Nat Immunol ,2003, 4: 825-826
269.Vines A, Wells K, Matrosovich M. The role of Influenza A virus hemagglutinin residues 226 and 228 in recep to r specificity and host range restriction. J Virol, 1998,72 (9): 7626-7631
270.Wang C B, Sun M, and Zhao T Z. Homology analysis of t he NS gene of H9N2 avian influenza virus isolates. Chinese J Prev Vet Med ,2004,26 (3): 177-180
271.Wang S, Shi W, Mweene A, Wei H, Bai G, Liu J H. Genetic analysis of the nonstructural (NS) genes of H9N2 chicken influenza viruses isolated in China during 1998-2002.Virus Gen, 2005,31(3):329-335
272.Wang X, Li M, Zheng H, Muster T, Palese P, Beg A A,Garcia-Sastre A. Influenza A virus NS1 protein prevents activation of NF-κB andinduction of alpha/beta interferon. J Virol,2000,74:11566-11573
273.Wang X, Li M, Zheng H, Muster T, Palese P, Beg A A, Garcia-SastreA. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J Virol, 2000,74,11566-11573
274.Washburn M P, Wolters D ,Yates J R.Large-scale analysis of the yeast proteome by multidimensional protein identification technology.Nat Biotech,2001,19(3):242-247
275.Wathelet M G,Lin C H, Parekh B S, Ronco L V,Howley P M, Maniatis T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell, 1998,2:507-518
276.Weiss A, Littman U R. Signal transduction by lymphocyte antigen receptor. Cell, 1999,76:263-268
277.Williams B R C. Transcriptional regulation of interferon-stimulated genes. Eur Biochem, 1991,200(1):1-11
278.Wolff T, O'Neill R E, Palese P. NS1-binding protein (NS1-BP): a novel human protein that interacts with the influenza A virus nonstructural NS1 protein is delocalized in the nuclei of infected cells. J Virol, 1998,72(9):7170-7180
279.Wolff T.O'Neill R E, Palese P. Interaction cloning of NS1-I, a human protein that binds to the nonstructural NS1 proteins of influenza A and B viruses. J Virol, 1996, 70(8): 5363-5372
280.Wood G W, McCauley J W, Bashiruddin J B, Alexander D J.Deduced amino acid sequences at the haemagglutinin cleavage site of avian influenza A viruses of H5 and H7 subtypes. Arch Virol, 1993, 130 (1/2): 209-217
281.Wu Y, Voth GA. A computational study of the closed and open states of t he influenza A M2 proton channel. Biophys J, 2005, 88 (4) :2402-2411
282.Wurze r W J, Planz O, Ehrhardt C, Giner M, Silberzahn T, Pleschka S, Ludwig S. Caspase 3 activation is essential for efficient influenza virus propagation.EMBO J, 2003,22:2717-2728
283.Xu X Y, Subbarao K, Cox N J, Guo Y J. Evaluation of genetically modified reassortant H5N 1 influenza A virus vaccine candidate generated by plasmid based reverse genetics. Virology, 2003,305:192-200
284.YangY P, Huang C T, Huang X P, Pardoll D M.Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat Immunol, 2004,5 (5): 508-515
285.Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K. Foy E. Loo Y M. Gale M Jr, Akira, S.Yonehara S, Kato A. Fujita T. Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity. J Immunol, 2005, 175: 2851-2858
286.Yoneyama M,Kikuchi M,Natsukawa T,Sbinobu N,Imaizumi T,Miya-gishi M. The RNA helicase RIG-1 has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol ,2004,5:730-737
287.Yu Q, Konig R, Pillai S, Chiles K. Single-strand specificity of APOBEC3G accounts forminus-strand deamination of the H IV genome. Nat Struct Mol Biol, 2004,11 (5): 435-442
288.Yuichi W, Akiko S,Kazufumi S, Takenori T ,Yoshinobu N.Stimulation of phagocytosis of influenza virus infected cells through surface desialylation of macrophages by viral neuraminidase. Microbiol Immunol, 2004, 48 (11):875-881
289.Zhirnov O P, Klenk H D. Control of apoptosis in influenza virus-infected cells by up-regulation of Akt and p53 signaling Apoptosis,,2007, 12:1419-1432
290.Zhirnov P, Konakova T E, Wolff T, Klenk H D.NS1 protein of influenza A virus down regulates apoptosis. J Virol, 2002,76(4):1617-1625
291.Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P,Lan N, Jansen R, Bidlingmaier S, Houfek T,Mitchell T, Miller P, Dean RA, Gerstein M, Snyder M. Global analysis of protein activities using proteome chips. Science, 2001,293(5537): 2101-2105
2.曹梅,田夫林,庄文忠.禽流感病毒血凝素分子生物学研究进展.动物医学进展,2004,25(2):35-37
3.曹永浩,张仕坚,周元聪.干扰素调节因子家族和免疫调控.生命的化学,2006,26(5):387-389
4.陈伯伦,张泽纪,陈伟斌.禽流感研究Ⅰ:鸡A型禽流感病毒的分离与血清学初步鉴定.中国兽医杂志,1994,22(10):3-5
5.陈宣烁,钟婉玲,郑小敏,张佩娟.禽流感病毒分子生物学的研究进展.中国畜牧兽医,2006,(33)1:63-67
6.程从升,李希妍,王琦,赵新生,黄晶晶,聂凯,张晓光,蓝雨,柳燕,张智清,舒跃龙,姚立红,温乐英,王大燕,王伟.H5N1亚型禽流感病毒安徽株NS1基因的克隆及在原核系统的表达.微生物学报,2007,47(3):418-422
7.褚小刚,杨占秋,龚作炯.新型抗病毒因子APOBEC3G研究进展.中国艾滋病性病,2006,12(6):577-579
8.邓扬,刘殿峰,王坤,张锐.禽流感病毒NS1A蛋白诱导人肺癌细胞SPC2A1的凋亡.中国生物制品学杂志,2007,20(11):821-824
9.甘孟侯.禽流感(第2版).北京:中国农业出版社,2002,30-79
10.关薇,王建,贺福初.大规模蛋白质相互作用研究方法进展.生命科学,2006,18(5):507-512
11.郭霄峰,廖明,辛朝安.H9N2亚型禽流感病毒的致病特性研究.华南农业大学学报,2001,22(7):70-72
12.郭元吉,李建国,程小雯,王敏,邹毅,李钏华,蔡访潺,瘳华乐,张烨,郭俊峰,黄瑞敏,贝东.禽H9N2亚型流感病毒能感染人的发现.中国实验和临床病毒学杂志,1999,13(2):105-108
13.郭元吉,温乐英,王敏,李梓,张烨,郭俊峰.我国猪群中H9N2亚型毒株HA 和NA基因特性的研究.中华实验和临床病毒学杂志,2004,18(1):7-11
14.郭元吉,温乐英,张烨,王敏,郭俊峰,李梓,舒跃龙.猪在禽H9N2亚型流感病毒感染人中的作用.中华实验和临床病毒学杂志,2005,19(2):106-109
15.郭志儒.荷兰暴发高致病性禽流感并出现人感染.中国兽医学报,2003,23(3):257
16.胡国斌,刘怡,邹群.流感病毒诱导宿主细胞凋亡的形态学观察.湖北工学院学报,2000,15(3):56-57
17.黄淑坚,廖明,辛朝安,苏广基.A Ⅳ致病分子基础的研究进展.动物医学进展,2004,25(3):1-3
18.贾因棠,魏来,蒋栋,丛旭,费然.干扰素刺激基因ISG20真核表达载体的构建及其抗丙型肝炎病毒复制作用的研究.中国免疫学杂志,2006,22(11):997-1001
19.蒋芳.浅谈我国禽流感疫情对家禽业的影响及建议.中国畜牧杂志,2006,42(10):25-26
20.蒋露芳,姜庆五.甲型流感病毒宿主特异性研究进展疾病控制杂志.2005,9(1):49-52
21.金伯泉.固有免疫中模式识别受体及其信号转导当代免疫学中最伟大的发现之一.细胞与分子免疫学杂志,2006,22(1):1-3
22.金梅花.H5N1亚型禽流感病毒感染雏鸡免疫器官免疫变化及机理.[硕士学位论文].沈阳:东北农业大学,2007
23.李建丽,张万坡,毕丁仁.A型流感病毒NS1蛋白研究进展.微生物学报,2007,47(4):729-733
24.李建伟.欧亚大陆H9N2亚型禽流感病毒分子演化的研究.[博士学位论文].哈尔滨:东北农业大学,2002
25.李玲.细胞凋亡的分子机制及其调控因子.国外医学免疫学分册,2002,25(6):317-320
26.李先茜,杜培革,傅桂莲,董婕,齐立.应用定点突变技术进行流感病毒NS1蛋白功能的研究.北华大学学报,2004,5(4):316-320
27.李向忠,方芳,陈则.流感病毒神经氨酸酶不同区域的作用.生命科学研究,2005,9(2):55-61
28.李新梅,陈汉春.干扰素调节因子家族.生命科学研究,2002,6(1):8-12
29.林祥梅.鸭源流感病毒人工感染鸡的病理学研究.[硕士学位论文].南京:南京农业大学,1998
30.刘光伟,夏雪培,赵勇.Toll样受体信号传导途径的研究进展.动物学杂志,2005,40(6):117-121
31.刘金华,史为民,吴清民,郭玉璞.我国部分鸡源H9N2亚型流感病毒NS1基因序列分析.微生物学报,2003,43(5):547-553
32.刘晓静,孙坚.流感病毒诱导细胞凋亡及抗流感药物的研究进展.实用临床医学,2007,8(1):136-138
33.刘秀梵.家养水禽在A型流感病毒和新城疫病毒进化和疾病流行中的作用.中国家禽,2007,29(15):1-7
34.龙进学,王曲直,刘秀梵.禽流感病毒NS第263～277位核苷酸缺失降低其抗干扰素能力.微生物学通报,2006,33(2):34-39
35.卢建红,邵卫星,龙进学,刘秀梵.A型流感病毒毒力因子研究进展.动物医学进展,2004,25(4):63-66
36.陆承平.高致病性禽流感与流感病毒.中国病毒学,2004,19(2):204-207
37.罗玲,胡薛英,程国富,谷长勤,周全,李自力,赵雅心,周诗其,毕丁仁.H9N2亚型禽流感病毒人工感染蛋鸡的组织病理学研究.中国预防兽医学报,2004,26(4):259-261
38.罗以勤,王梁华,马玲,孔建新,焦炳华.细菌双杂交系统筛选与tumstatin45-132相互作用蛋白质.中华微生物与免疫学杂志,2007,27(2):101-106
39.马春全,赵德明,黄兴国,黄淑坚,卢玉葵.鹅高致病性禽流感病理组织学观察.中国预防兽医学,2006,28(2):175-177
40.彭开松,佘锐萍.动物病毒与宿主细胞的细胞凋亡.中国兽医杂志,2004,40(11):42-44
41.冉旭华,崔玉东,朴范泽.病毒感染与细胞凋亡.动物医学进展,2003,24(4):22-25
42.任仙文,李北平,王月兰,岳俊杰,梁龙.蛋白质相互作用的生物信息学研究进展.生物技术通讯,2006,17(6):976-980
43.萨姆布鲁克,拉塞尔.分子克隆实验指南(第三版).(黄培堂等 译).北京:科学出版社,2002,1481-1486
44.宋卉.雏鸵鸟免疫器官的形态学特点及鸡源NDV对雏鸵鸟致病机理的研究.[博士学位论文].武汉:华中农业大学,2007
45.孙博兴.H9N2亚型禽流感非结构蛋白NS1A基因的克隆表达及其诱导Hela细胞凋亡的研究.[博士学位论文].长春:吉林大学,2005
46.孙进华,吴明福,邢明伟,靳淼,王君伟.A型流感病毒非结构蛋白的功能及临床应用.生物化学与生物物理进展,2006,33(8):724-729
47.孙颖杰.禽流感研究进展.国外兽医学—畜禽传染病,1998,18(1):19-22
48.唐秀英,于康震,田国斌,赵传删.中国禽流感流行株的分离鉴定.中国畜禽传染病,1998,20(1):1-5
49.万春和,刘明.A型流感病毒M2蛋白研究进展.动物医学进展,2007,28(7):56-60
50.王艾琳,李坚.病毒与细胞凋亡.自然杂志,2004,26(3):125-128
51.王海波,安学丽,张艳贞,王爱丽,李巧云,晏月明.蛋白质相互作用研究方法及其应用.生物技术通报,2006(suppl):167-170
52.王海坤,韩代书.Toll样受体(TLRs)的信号转导与免疫调节.生物化学与生物物理进展,2006,33(9):820-827
53.王坤.禽流感病毒NS1A重组蛋白联合黄芩苷抗肿瘤作用研究.[博士学位论文].长春:吉林大学,2007
54.王忠田.1999-2000意大利禽流感的回顾.动物医学进展,2003,23(2):75
55.吴波,周晓军.细胞凋亡检测技术进展及其应用.临床实验病理学杂志,1997,8(3):262-264
56.吴志豪,王建,贺福初.大规模酵母双杂交技术研究蛋白质相互作用的应用.遗传,2006,28(12):1627-1632
57.谢月萍,刘鑫,叶进,江军,侯晓华.抗病毒分子APOBEC3G的研究进展.中西医结合肝病杂志,2007,17(4):255-257
58.淹泽刚.流感病毒感染与细胞凋亡.日本医学介绍,2004,25(9):411-412
59.杨齐衡,李林.酵母双杂交技术及其在蛋白质组研究中的应用.生物化学与生物物理学报,1999,31(3):221-225
60.杨涛,杜绍范,刘明.A型流感病毒NS1蛋白研究进展.现代畜牧兽医,2005,3:43-45
61.杨玉荣,佘锐萍,梁宏德.Toll-NF-kB信号途径及其介导的功能.细胞生物学杂志,2007,29:483-486
62.叶慧燕,熊思东.RIG-I介导的TLR非依赖性模式识别.生命的化学,2007,27(4):302-304
63.尹彦涛,夏平安,崔保安,赵云航,王建举,党占国,柴春霞.MxA抗病毒蛋白的研究概况.中国畜牧兽医,2008,35(1):87-89
64.于康震,崔尚金,付朝阳,唐秀英.禽流感与养禽业发展和人类健康.中国预防兽医学报,2000,22(4):313-315
65.于康震,付朝阳,崔尚金,步志高,唐秀英.我国禽流感防制研究进展.中国兽医学报,2001,21(1):103-106
66.余丹丹.两株H5N1亚型禽流感病毒诱导的细胞凋亡研究.[硕士学位论文].南京:南京农业大学,2005
67.张春斌,宋汉君,刘东璞.细胞凋亡与病毒感染.黑龙江医药科学,2004,27(6):63-64
68.张衡,李康生.流感病毒与细胞凋亡.微生物学免疫学进展,2007,35(2):76-78
69.张瑞莉,葛铭,张草,郑世民.鹅源H5N1亚型禽流感病毒感染雏鸡免疫器官的病理学观察.中国兽医科学,2007,37(4):333-337
70.张万坡.禽流感病毒感染鸡的抗原定位及基因差异表达研究.[博士学位论文].武汉:华中农业大学,2006
71.张泽纪,陈伯伦.禽流感研究Ⅱ:禽流感的发生情况和血清学调查.中国兽医杂志,1994,20(10):6-7
72.张志珍,段炼,李康生.华南流感病毒NS1基因特性研究.生物化学与生物物理进展,2004,31(3):237-243
73.张卓.H5N1亚型禽流感病毒感染雏鸡的病理学变化及其发生机制.[硕士学位论文].沈阳:东北农业大学,2007
74.赵明才,唐恩洁,朱道银.与细胞凋亡相关的细胞凋亡分子.国外医学病学分册,2000,8(1):25-29
75.赵仁亮.细胞凋亡的检测方法.医学综述,2002,8(3):130-131
76.郑丽舒,段招军.A型流感病毒M2蛋白疫苗的研究进展.病毒学报,2006,22(6):487-491
77.周晓娜.RIG-I信号转导途径在机体抗病毒中的作用.生命的化学,2007,27(5):381-383
78.朱建国.A型流感病毒基质蛋白研究进展.动物医学进展,2004,25(2):24-26
79.Akira S,Takeda K.Toll-like receptor signaling.Nat Rev Immunol,2004,4(7):499-511
80.Aleksandr S,Lipatov,Andreansky S,Webb y R J,Huls e DJ,Rehg J E,KraussS,Perez1 D R,Doherty P C,Webster R G,Sangster MY.Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice:the role of cytokines and B- and T-cell responses.J Gen Virol,2005,86(4):1121-1301
81.Alexander D J,Senne D A.Avian influenza in the Western Hemisphere including the Pacific Island and Australia.Avian Dis,2003,47:789-805
82.Alexander D J.A review of avian influenza in different bird species.Proceedings of the ESVV Symposium on animal influenza viruses,Gent.1999,Vet Microbiol,2000,74:3-13
83.Amonsin A,Payungpom S,Theamboonlers A.Genetic characterization of H5N1influenza A viruses isolated from zoo tigers in Thailand.Virology,2006,344(2):480-491
84.Aragon T,Luna Susana de la,Novoa,CarrascoL,Ortin J,Nietol A.Eukaryotic translation initiation factor 4GI Is a cellular target for NS1 Protein:a translational activator of influenza virus.Mol Cel Biol,2000,20(17):6259-6268
85.Avalos,Yu Z,Nayak D P.Association of influenza virus NP and M1 proteins with cellular cytoskeletal elements in influenza virus infected cells.Virology,1997,71:2947-2958
86.Baigent S J,Mccauley J W.Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture.Virus Res,2001,79(1-2):177-185
87.Banet-Noach C,Panshin A,Golender N,Simanov L,Rozenblut E,Pokamunski S,Pirak M,Tendler Y,Garcia M,Gelman B,Pasternak R,Perk S.Genetic analysis of nonstructural gene(NS1 and NS2) of H9N2 and H5N1 viruses recently isolated in Israel.Virus Gen,2007,34(2):157-168
88. Banks J,Speidel E S, Moore E, Plowright L, Piccirillo A,Capua I,Cordioli P,Fioretti A,Alexander D J.Changes in the haemagglutinin and the neuraminidase genes prior to the emergence of highly pathogenic H7N1 avian influenza viruses in Italy. Arch Virol, 2001, 146 (5): 963-973
89. Basler C F,Reid A H, Dybing J K, Janczewski T A, Fanning T G, Zheng H, Salvatore M,Perdue M L,Swayne D E,Garcia-Sastre A. Palese P, Taubenberger J K.Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes.PNAS, 2001,98 (5):2746-2751
90. Bass B L, Nishikura K, Keller W,Seeburg P H, Emeson R B, O'Connell M A, Samuel C E, Herbert H. A standardized nomenclature for adenosine deaminases that act in RNA.RNA, 1997, 3: 947-949
91. Bergmann M, Garcia-SastreA, Carnero E, Pehamberger H, Wolff K, Palese P, Muster T. Influenza Virus NS1 protein counteracts PKR-mediated inhibition of replication. J Virol, 2003, 74 (13): 6203-6206
92. Bornholdt Z A, Prasad B V.X-ray structure of influenza virus NS 1 effector domain. Nat Struct Mol Biol, 2006,13(6):559-560
93. Bridges C B, Lim W, Hu-Primmer J, Sims L,Fukuda K,Mak K H,Rowe T, Thompson W W,Conn L,Lu X,Cox N J,Katz J M.Risk of influenza A (H5N1) infection among poultry workers, Hong Kong ,1997-1998. J Infect Dis, 2002,185 (8) :1005-1010
94. Brown EG.Influenza Virus genetics.Biomed & Pharmacother 2000,54:196 -209
95. Browne E P, Wing B,Coleman D,Shenk T. Altered cellular mRNA levels in human cytomegalovirus-infected fibroblasts: viral block to the accumulation of antiviral mRNAs. J Virol, 2001, 75: 12319-12330
96. Brydon E W A,Smith H,Sweet C. Influenza A virus induced apoptosis in bronchiolar epithelial (NCI2H292) cells limits pro-inflammatory cytokine release. J Gen Virol 2003,84: 2389-2400
97. Burgui I, Aragon T, Ortin J, Nieto A.PABP1 and eIF4GI associate with influenza virus NS1 protein in viral mRNA translation initiation complexes. J Gen Virol, 2003, 84:3263-3274
98. Cameron K R, Gregory V, Banks J, Brown I H, Alexander D J, Hay A J,LinY P. H9N2 subtype influenza A viruses in poultry in Pakistan are closely related to the H9N2 viruses responsible for human infection in Hong Kong. Virology,2000,278:36-41
99. Castrucci M R, Kawaoka Y.Biologic importance of neuraminidase stalk length in influenza A virus. J Virol, 1993,67 (2): 759-764
100. Causier B,Davies B. Analysing protein-protein interactions with the yeast two-hybrid system. Plant Mol Biol, 2002,50(6): 855-870
101. Chanturiya A N, Basanez G,Schubert U, Nenklein P,Yewdell J W,Zimmerberg J.PB1-F2,an influenza A virus-encoded proapoptotic mitochondrial protein, creats variably sized pores in planar lipid membranes. J Virol, 2004, 78(12):6304-6312
102.Chen H, Bright R A, Subbarao K,Smith C, Cox N J, Katz J M, Matsuoka Y.Polygenic virulence factors involved in pathogenesis of 1997 Hong Kong H5N1 influenza viruses in mice. Virus Res, 2007, 128: 159-163
103.Chen J, Lee KH, Steinhauer D A, Stevens D J, Skehel J J,Wiley D C. Structure of the haemagglutinin precursor cleavage site.a determinant of influenza pathogenicity and the origin of the labile conformation.Cell, 1998,95: 409-417
104.Chen W, Calvo P A, Malide D, Gibbs J, Schuber U, Bacik I, Basta S, O'Neill R, Schickli J, PaleseP, Henklein P, Bennink J R, Yewdell J W. A novel influenza A virus mitochondrial protein that induces cell death. Nat Medicine, 2001, 7 (12): 1306-1312
105.Chen Z, Li Y, Krug R M. Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 39-end processing machinery. EMBO J,1999,18(8): 2273-2283
106.Chien CY, XuY, Xiao R,Aramini J M, Sahasrabudhe PV, Krug R M, MontelioneG T. Biophysical characterization of the complex between double-stranded RNA and the N-terminal domain of the NS1 protein from influenza A virus: evidence for a novel RNA-binding mode. Biochemistry, 2004,43(7): 1950-1962
107.Choi Y K, Ozaki H, Webby R J,Webster R G, Peiris J S ,Poon L, Butt C,Leung Y H, Guan Y.Continuing evolution of H9N2 influenza viruses in South eastern China. Virology, 2004, 78 (16) :8609-8614
108.Colamussi M L, White M R,Crouch E,Hartshonn K L. Influenza A virus accelerates neutrophil apoptosis and markedly potentiates apoptotic effects of bacteria. Blood, 1999,93 (7):2395-2403
109.Czabotar P E,Martin S R, Hay A J.Studies of structural changes in t he M2 proton channel of influenza A virus by tryptophan fluorescence. Virus Res,2004,99 (1) :57261
110.De L S,Bartolome J,Carreno V.Hepatitisc virus core protein down-regulates transcription of interferon-induced anti-ral genes.J Infect Dis,2005,191 (1) :93-99
111. Der S D,Zhou A, Williams B R G, Silverman H. Identification of genes differentially regulated by interferon α, β or γ using oligonucleotide arrays.PNAS USA, 1998,95, 15623-15628
112.Dundon W G,Milani A,Cattoli G,Capua I.Progressive truncation of the Non-Structural 1 gene of H7N1 avian influenza viruses following extensive circulation in poultry, Virus Res, 2006, 119(2): 171-176
113.Duong-Ly K C, Nanda V, Degrado W, Howard K P. The conformation of the pore region of t he M2 proton channel dependson lipid bilayer environment. Protein Sci, 2005,14(4):856-861
114.Ehrhardt C, Wolff T, Pleschka S, PlanzO, Beermann W, Bode J G, Schmolke M, LudwigS.The influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate antiapoptotic signaling responses. J Virol,2007,81(7):3058-3067
115.Ellis A E. Innate host defense mechanisms of fish against viruses and bacteria. Dev Comp Immunol, 2001,25: 827-839
116. Ellis T M, Bousfield B, Bissett L, Dyrting K, Luk G S M, Tsim S T, Sturm-Ramirez K, Webster R G, Guan Y, Peiris M J S.Investigation of outbreaks of highly pathogenic H5N1 avian influenza in waterfowl and wild birds in Hong Kong in late 2002, Avian Pathol, 2003, 33:492-505
117.Enami K, Sato T A, Nakada S. Influenza virus NS1 protein stimulates translation of the M1 protein, J Virol, 1994,68: 1432-1437
118.Enami M, Enami K. Characterization of Influenza virus NS1 protein by using a novel helper-virus-free reverses genetic system. J Virol,2000,74(12): 5556-5561
119.Esnault C, Millet J, Schwartz O, HeidmannT.Dual inhibitory effects of APBOEC family proteins on retrotransposition of mammalian endogenous retroviruses. Nucleic Aacids Res, 2006,34 (5): 1522-1531
120.Espert L, Degols G,Gongora C, Blondel D,Williams B R, Silverman R H,Mechti N. ISG20, a new interferon induced RNase specific for single-stranded RNA, defines an alternative antiviral pathway against RNA genomic viruses. J Biological Chemistry, 2003, 278 (18): 16151-16158
121.Fagerstam LG,Frostell-Karlsson A, Karlsson R, Persson B,Ronnberg I. Biospecific interaction analysis using SPR detection applied to kinetic, binding site and concentration analysis. J Chromatogr, 1992,597: 397- 410
122.Falcon A M, Fortes P, Marion R M, Beloso A, Ortin J. Interaction of influenza virus NS1 protein and the human homologue of Staufen in vivo and in vitro. Nucleic Acids Res,1999,27(11):2241-2247
123.Falcon A M, Marion R M, Zurcher T, Gomez P, Portela A, Nieto A, Ortinl J.Defective RNA replication and late gene expression in temperature-sensitive Influenza viruses expressing deleted forms of the NS1 protein J Virol, 2004,78(8):3880-3888
124.Femandez-SesmaA, Marukian S, Ebersole B J, Kaminski D, Park M S, Yuen T, Sealfon S CGarcfa-Sastre A ,Moran T M. Influenza Virus Evades Innate and Adaptive Immunity via the NS1 Protein. J Virol, 2006,80(13): 6295-6304
125.Fields S, Song O K. A novel genetic system to detect protein-protein interactions. Nature, 1989,340(6230): 245-246
126.Fouchier R A, Munster V, Wallensten A,Bestebroer T M,Herfst S, Smith D, Rimmelzwaan G F, Olsen B, Osterhaus A D. Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol, 2005 ,79 (5) :2814-2822
127.Gambaryan A S, Robertson J S, Matrosovich M N. Effects of egg-adaptation on the receptor-bingding properties of human influenza A and B viruses. Virology, 1999, 258 (2): 232-239
128.Gambaryan A S, Tuzikov A B, Piskarev V E.Specification of receptor-binding phenotypes of influenza virus isolates from different hosts using synthetic sialylglycopolymers: non-egg-adapted human H1 and H3 influenza A and influenzaB viruses share a common high binding affinity for 6'-sialy (Nacetyllac-tosamine). Vi rology, 1997, 232 (2):345-350
129.Geiss G K,Salvatore M, Tumpey T M,Carter V S,Wang X,Basler C F,Taubenberger J K,Bumgarner R E, Palese P, Katze M G,Garcia-Sastre A. Cellular transcriptional profiling in influenza A virus-infected lung epithelial cells: the role of the nonstructural NS1 protein in the evasion of the host innate defense and its potential contribution to pandemic influenza.PNAS, 2002,99(16): 10736-10741
130. George C X and Samuel C E.Human RNA specific adenosine deaminase ADAR1 transcripts possess alternative exon 1 structures that initiate from different promoters, one constitutively active and the other interferon-inducible. PNAS USA, 1999,96: 4621-4626
131.Gjermandsen I M, Justesen J, Martensen P M.The interferon-induced gene isg12 is regulated by various cytokines as the gene 6-16 in human cell lines. Cytokine, 2000,12(3): 233-238
132.Gong J,Xu W,Zhang J.Structure and functions of influenza virus neuraminidase. Curr Med Chem,2001 , 14 (1): 113-122
133.Goto H, Kawaoka Y. A novel mechanism for the acquisition of virulence by a human influenza A virus. PNAS USA, 1998, 95: 10224-10228
134.Gougeon M L, Motagnier L. Apoptosis in AIDS. Science, 2002,260:1269-1272
135.Guan.Y,Shortridge K F,Krauss S,Webster R G. Molecular characterization of H9N2 influenza viruses: were they the donors of the"internal"genes of H5N1 viruses in Hong Kong? PNAS USA, 1999, 96(16):9363-9367
136.Gubareva LV, Kaiser L, Hayden FG.Influenza virus neuraminidase inhibitors. Lancet ,2000,355 (9206) :827-835
137.Guo Y J,Krauss S, Senne D A,Senne D A, Mo I P,Lo K S. Characterization of the pathogenicity of the member of the newly established H9N2 influenza virus lineages in avian.Virology,2000, 269(1):278-288
138.Hacker H, Redecke V, Blagoev B, Kratchmaroval, Hsu L C, Wang G G, KampsEyal Raz M P, WagnerH, Hacker G, Mann M , Karin M. Specificity in Toll-like receptor signalling through distinct effector functions of T RAF3 and TRAF6, Nature, 2006, 439 (7073): 204-207
139.Hale B G, JacksonD, Chen Y H, Lamb RA, Randall R E. Influenza A virus NS1 protein binds p85β and activates phosphatidylinositol-3-kinase signaling. PNAS USA, 2006, 103: 14194-14199
140.Haller O, Kochs G. Interferon-induced Mx proteins: dynamin-like GTPases with antiviral activity. Traffic,2002,3(10):710-714
141.Harada H, Takahashi E I.Structure and regulation of the human interferon regulatory factor 1 and IRF 2 genes; implication for a gene network in the interferon system. Mol Cell Biol, 1994, 14(2): 1500-1509
142.Harvey B P,Banga S S, Ozer H L, Regulation of the multifunctional Ca2+/ calmodulin-dependent protein kinase II by the PP2C phosphatase PPM1F in fibroblasts. J Biol Chem,2004, 279 (23): 24889-24898
143.Hatta M, GaoP, Halfmann P, Kawaoka Y.Molecular basis for high virulence of Hong Kong H5N1 influenza A vieuses. Science,2001, 293: 184021842
144.Hayman A,Comely S,Lackenby A,Hartgroves L CGoodbourn S,McCauley J W,Barclay W S. NS1 protein of avian Influenza A virus can act as antagonist of the human alpha/beta interferon response. J Virol, 2007, 81(5):2318-2327
145.Hechtfischer A, Marschall M, Helten A, Boswald C, Meier-Ewert H. A highly cytopathogenic influenza C virus variant induces apop tosis in cell culture. J Gen Virol ,1997,78: 1327-1330
146.Heim M H. RIG-I: an essential regulator of virus-induced interferon production.J Hepatol,2005, 42:431-433
147.Hinshaw V S, Olsen C W, Sissoko N D , Evans D. Apoptosis: a mechanism of cell killing by influenza A and B viruses .J Virol, 1994,68: 3667-3673
148.Homme P J, Easterday B C.Avian influenza virus infection. I.Charaterization of an influenza A/Turkey/Wisconsim/1966 virus, Avian Dis, 1970, 14:66-74
149.Horimoto T, Kawaoka Y. Reverse genetics provides direct evidence for a correlation of hemagglutinin cleavability and virulence of an avian influenza A virus. J Virol, 1994,68 (5): 3120-3128
150.Horimoto T,Kawaoka Y. Pandemic threat posed by avian influenza A viruses.Clin Microbiol Rev, 2001, 14(1): 129-149
151.Horio T, Murai M, Inoue T, Hamasaki T, Tanaka T, Ohgi T.Crystal structure of human ISG20, an interferon induced antiviral ribonuclease. FEBS Letters, 2004,577 (122): 111-116
152.Hornickova Z.Different progress of MDCK cell death after infection by two different influenza virus isolates. Cell Biochem Funct, 1997,15: 87-93
153.Hornung V, Ellegast J, Kim S, Brzozka K, Jung A, Kato H,Poeck H,Akira S,Conzelmann K K,Schlee M,Endres S,Hartmann,G.5-prime-triphosphate RNA is the ligand for RIG-I. Science , 2006,314:994-997
154.Hoshino K, KaishoT, Iwabel T, Takeuchil O , Akira S. Differential involvement of IFN-beta in Toll-like receptor-stimulated dendritic cell activation. Int Immunol, 2002,14(10): 1225-1231
155.Hu J C, Kornacker, Cx M, Hochschild A. Escherichia coli one- and two-hybrid systems for the analysis and identification of protein-protein interactions. Methods, 2000,20(1): 80-94
156.Huang Q, Liu D, Majewski P, Schulte L C, Korn J M Young, R A, Lander E S, HacohenN.The plasticity of dendritic cell responses to pathogens and their components. Science, 2001, 294 (5543): 870875
157.Huh W K, Falvo J V,Gerke L C, Carroll A S,Howson R W,Weissman J S, O'Shea E K.Global analysis of protein localization in budding yeast. Nature, 2003,425(6959): 686-691
158.Ito T, Kobayashi Y,Morita T,Horimoto T, Kawaoka Y. Virulent influenza A Viruses induce apoptosis in chickens. Virus Res, 2002,84:27-35
159.Iwasaki A, Medzhitov R. Toll-like receptor control of the adaptive immune responses. Nat Immunol, 2004, 5 (10): 987-995
160.Jackson D, Hossain M J, Hickman D, Perez D R, Lamb R A. A new influenza virus virulence determinant: The NS1 protein four C-terminal residues modulate pathogenicity. PNAS USA, 2008,105(11):4381-4386
161.Jeffrey I W,Bushell M, Tilleray V J,Morley S, Clemens M J. Inhibition of protein synthesis in apoptosis: differential requirements by the tumor necrosis factor a and a DNA-damaging agent for Caspases and the double-stranded RNA-dependent protein kinase.Cancerr Res, 2002, 62: 2272-2280
162.Kaisho T, Akira S. Toll-like receptor function and signaling. J Allergy Clin Immunol, 2006,117 (5): 979-987
163.Kamille C J,Smidt, HansenL L, Sogaard T M, Petersen L K, Knudsen U B, Martensen P M. A nine-nucleotide deletion and splice variation in the coding region of the interferon induced ISG12 gene. Biochimica et Biophysica Acta,2003,1638: 227- 234
164.Kasper H, Janssen E M, Kim S O, Alexopoulou L, Flavell R A, Han J, Beutler B. Upregulation of costimulatory molecules induced by lipopolysaccharide and double-stranded RNA occurs by Trif-dependent and Trif-independent pathways. Nat Immunol, 2003,4 (12): 1223 -1229
165.Kass, Arkin T. How pH opens a H~+ channel: the gating mechanism of influenza A M2 .St ructure, 2005 ,13 (12): 1789-1798
166.Kawaoka Y, Naeve C W, Webster R G. Is virulence of H5N 2 influenza viruses in chickens associated with loss of carbohydrate from the hemagglutinin? Virology, 1984,139 (2): 303-316
167.Keawcharoen J, Oraveerakul K, Kuiken T,Fouchier R A,Amonsin A.Payungporn S.Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis, 2004, 10: 2189-91
168.Khatchikian D, Orlich M, Rott R. Increased viral pathogenicity after insertion of a 28S ribosomal RNA sequence into the haemagglutinin gene of an influenza virus. Nature, 1989,340: 156-157
169.Kiyoko I H, Taisuke H, Yutaka F, Yoshihiro K. Generation of influenza A virus NS2 (NEP) mutants with an altered nuclear export signal sequence. J Virol, 2004,78 (18): 10149-10155
170.Klenk H D, Ohuchi M, OhuchiR, Konig G, Angliker H, Shaw E, Stieneke-Grober A, Vey M, Garten W.Proteolytic activation as a determinant for the pathogenicity of influenza viruses: substractes and proteases,Proc 3rd Int Symp A vian Influenza.Madison: University of Wisconsin Press, 1992:182-198
171.Knapp S, Yeel J, Frodshama J, Hennig B J W, Hellier S, Zhang L, Wright M, Chiaramonte M, Graves M, Thomas H C,Hill AVS, Thursz M R. Polymorphisms in interferon-induced genes and the outcome of hepatitis C virus infection : roles of MxA, OAS and PKR.Genes Immun,2003 ,4(6) :411-419
172.Koh C G, Tan E J, Manser E, Lim L. The p21 -activated kinase PAK is negatively regulated by POPX1 and POPX2, a pair of serine/threonine phosphatases of the PP2C family. Curr Biol ,2002,12 (4): 317-321
173.Krug R M, Yuan W, Noah D L, Latham A G. Intracellular warfare between human influenza viruses and human cells: the roles of the viral NS1 protein. Virology,2003,309(2): 181 -189
174.Kuiken T, Rimmelzwaan G, van Riel D,van Amerongen G, Baars M, Fouchier R. Avian H5N1 influenza in cats. Science, 2004,306: 241
175.Labrada L, LiangX H, Zheng W, JohnstonC, LevineB. Age-Dependent Resistance to Lethal Alphavirus Encephalitis in Mice: Analysis of Gene Expression in the Central Nervous System and Identification of a Novel Interferon-Inducible Protective Gene, Mouse ISG12. J Virol,2002,76(22): 11688-11703
176.Lamb R A, Choppin P W. Segment 8 of the influenza virus genome is unique in coding for two polypeptides. PNAS USA ,1979,76:4908-4912
177.Lemaitre B.The road to Toll. Nat Rev Immunol, 2004,4 (7): 521-527
178.U C, Yu K,Tian G,Yu D,Liu L, Jing B, Ping J, Chen H . Evolution of H9N2 influenza viruses from domestic poultry in Mainland China. Virology,2005,340 (1):70-83
179.Li K S, Xu K M, Peiris J S M, Poon L L M, Yu K Z, Yuen K Y, Shortridge K F, Webster R G, Guan Y.Characterization of H9 Subtype Influenza Viruses from the Duck of Southern China :a Candidate for the Next Influenza Pandemic in Humans? J Virol ,2003,77:6988-6994
180.Li X D, Sun L, Seth R B, Pineda G, Chen Z J.Hepatitis C virus protease NS3/4A cleaves mitochondrial antiviral signaling protein off the mitochondria to evade innate immunity. PNAS USA ,2005,102:17717-17722
181.Li Y, Chen Z Y, Wang W, Bake r C C, Kru g R M. The 3'-end-processing factor CPSF is required for the splicing of single-intron pre-mRNAs in vivo.RNA,2001, 7(6): 920-931
182.Li Z, Jiang Y, Jiao P, Wang A, Zhao F, TianG, Wang X, Yu K, Bu Z, ChenH.The NS1 gene contributes to the virulence of H5N1 avian influenza viruses. J Virol, 2006,80(22): 11115-11123
183.Liew F Y, Xu D,Brint E K, O'Neill L A.Negative regulation of toll-like receptor-mediated immune responses. Nat Rev Immuno, 2005, 5(6): 446-458
184.Lin C B, Zimmer S G, Lu Z J, Holland R E, Dong Q, Chambers T M. The involvement of a stress activated pathway in equine influenza virus-mediated apoptosis. Virology,2001,287: 202-213
185 .Lin Y P, Shaw M, Gregory V,Cameron K, Lim W, Klimov A, Subbarao K, Guan Y, Krauss S,Shortridge K, Webster R, Cox N,Hay A. Avian-to-human transmission of H9N2 influenza A viruses: relationship between H9N2 and H5N1 human isolate, PNAS USA , 2000, 97(17):9654-9658
186.Lipatov A S, Andreansky S, Webby R J, Hulse D J, Rehg J E, Krauss S, Perezl D R, Doherty P C, Webster R G , Sangster M Y.Pathogenesis of Hong Kong H5N1 influenza virus NS gene reassortants in mice: the role of cytokines and B- and T-cell responses. J Gen Virol, 2005, 86 (4): 1121-11301
187.Liu J H, Okazaki K, Shi W M, Wu Q M, MweeneA S, Kida H. Phylogenetic analysis of neuraminidase gene of H9N2 influenza viruses prevalent in chickens in China during 1995-2002. Virus Gen, 2003,27(2): 197-202
188.Liu J, Lynch P A, Chien C Y, Montelione G T, Krug R M,Berman H M. Crystal structure of the unique multifunctional RNA binding domain of the influenza virus NS1 protein. Nat Struct Biol, 1997,4(11): 896-899
189.Liu T, Ye Z. Alteration of the basic amino acid domain of wild-type matrix protein reduced influenza virus rep lication at non-permissive temperature. Int Congr Ser, 2004, 1263: 83-89.
190.Lommer B S, Luo M. Sructural plasticity in Influenza virus protein NS2 (NEP). J Biol Chem, 2002,277 (9):7108-7117
191.Ludwig S, Schultz U, Mandler J, Fitch W M, Scholtissek C.Phylogenetic relationship of the nonstructural (NS) genes of influenza A viruses.Virology, 1991,183(2): 566-577
192.Ludwig S, Wang X, Ehrhardt C, Zheng H, Donelan N, Planz O, Pleschka S, Garcia-Sastre A, Heins G, WolffT.The influenza A virus NS1 protein inhibits activation of Jun N-Terminal kinase and AP-1 transcription factors. J Virol, 2002, 76: 11166-11171
193 .Marion R M, Zurcher T, Luna S de la, Ortin J. Influenza virus NS1 protein interacts with viral transcription-replication complexes in vivo. Gen Virol, 1997,78 :2447-2451
194.Martensen P M, Sogaard T M M, Gjermandsen I M, Buttensch0n H N, Rossing A B, Bonnevie-Nielsen V, Rosada C, Simonsen J L, Justesen J. The interferon alpha induced protein ISG12 is localized to the nuclear membrane.. Eur J Biochem, 2001, 268: 5947-5954
195.Matrosovich M,Tuzikov A, Bovin N, Gambaryan A, Klimov A, Castrucci M R, Donatelli I,Kawaoka Y. Early alterations of the receptor binding properties of H1, H2 and H3 avian influenza virus hemagglutinins after their introduction into mammals J Virol, 2000, 74 (18): 8502-8512
196.Matrosovich M,Zhou N, Kawaoka Y, Webster R. The surface glycoprotein of H5 Influenza viruses isolated from humans,chickens,and wild aquatic birds have distinguished properties J Virol, 1999,73 (2): 1146-1155
197.McCullers J A, Bartmess K C. Role of neuraminidase in lethal synergism between influenza virus and Streptococcus pneumonia.J Infect Dis, 2003 ,187(6): 1000-1009
198.Meylan E .Tschopp J.Toll-Like Receptors and RNA Helicases: Two parallel ways to triggerantiviral responses Molecular cell, 2006,22(5):561-569
199.Mibayashi M, Martinez-Sobrido L, Loo Y M, Cardenas W B, Gale MJr, Garcia-Sastre A. Inhibition of retinoic acid-inducible gene I-mediated induction of beta interferon by the NS1 protein of influenza A virus.J Virol, 2007,81: 514-524
200.Mikhail N, Krauss M S.H9N2 influenza A viruses f rom poultry in Asia have human virus-like receptor specificity. Virology,2001,281 (2): 156-162
201. Min J Y, Krug R M.The primary function of RNA binding by the influenza A virus NS1 protein in infected cells:Inhibiting the 2'-5' oligo (A) synthetase/RNase L pathway. PNAS, 2006, 103(18):7100-7105
202.Min J Y, Li S, Sen G C.A site on the influenza A virus NS1 protein mediates both inhibition of PKR activation and temporal regulation of viral RNA synthesis. Virology,2007,363:236-243
203.Mo I P, Brugh M, Fletcher O J.Rowland G N, Swayne D E.Comparative pathology of experimentally inoculated with avian influenza viruses of low and high pathogenicity. Avian Dis, 1997,41:125-1361
204.Mori I, Komatsu T, Takeuchi K, Nakakuki K, Sudo M, Kimura Y. In vivo induction of apoptosis by influenza virus. J Gen Virol, 1995,76(ptl 1):2869-2873
205.Mossman K L,Macgregor P F,Rozmus J J,Goryachev A B, Edwards A M, Smiley J R. Herpes simplex virus triggers and then disarms a host antiviral response. J Virol, 2001,75: 750-758
206.Nakajima K, Nobusawa E, Nakajima S. Volution of the NS genes of the influenza A viruses. Ⅱ. The genetic relatedness of the NS genes of animal influenza viruses. Virus Genes, 1990,4(1): 15-26
207. Nakajima K.The mechanism of antigenic shift and drift of human influenza virus. N ippon Rinsho,2003,61 (11): 1897-905
208.Navarro F, Bollman B, Chen H, Konig R,Yu Q, Chiles K,Landau NR.Complementary function of the two catalytic domains of APOBEC3G. Virology,2005,333 (2 ):374-386
209.Nemeroff M E, Barabino S M, Li Y,Keller W, Krug R M. Influenza virus NS1 protein interacts with the cellular 30 kDa subunit of CPSF and inhibits 3'end formation of cellular pre-mRNAs. Mol Cell/,1998,1(7):991-1000
210.Neumann G, Hughes M T, Kawaoka Y. Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1.EMBO J, 2000,19(24):6751-6758
211.Nguyen L H, Espert L,Mechti N,Wilson D M 3rd. The human interferon- andestrogen-regulated ISG20/HEM45 gene product degrades single-stranded RNA and DNA in vitro. Biochemistry, 2001, 40: 7174-7179
212.Nichols J E, Niles J A, Roberts N J J r.Human lymphocyte apoptosis after exposure to influenza A virus.7 Virol, 2001, 75(13): 5921-5929
213.Obenauer J C, Denson J, Mehta P K, Su X, Mukatira S, Finkelstein D B, XuX, Wang J, Ma J, Fan Y, Rakestraw K M, Webster RG, Hoffmann E, KraussS, Zheng J, Zhang Z, Naeve C W. Large-scale sequence analysis of avian influenza isolates.Science, 2006,311:1576-1580
214.Ohuchi M, Asaoka N, Sakai T.Roles of neuraminidase in the initial stage of influenza virus infection. Microbes Infect, 2006,8 (5): 1287-1293
215.O'Neill R E, Talon J, Palese P.The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J,1998,17,288-296
216.Opitz B, Rejaibi A, Dauber B, Eckhard J,Vinzing M, Schmeck B, Hippenstiel S, Suttorp N,Wolff T. IFN-β induction by influenza A virus is mediated by RIG-I which is regulated by the viral NS1 protein. Cell Microbiol,2007, 9(4):930-938
217.Pasare C, Medzhitov R.Control of B-cell responses by Toll-like receptors. Nature,2005, 438 (7066): 364-368
218.Peiris M,Guan Y,Markwell D,Ghose P,Webster R C, Shortridge K F.Cocirculation of H9N2 and contemporary "human"influenza A viruses in pigs in southeastern China: Potential for genetic reassortment. J Virol,2001,75(20):9679-9686
219.Peiris M,Yam W C, Leung C W, Chan K H, Ip P L, Lai R W, Orr W K, Shortridge K F.Human infection with influenza H9N2. Lancet, 1999, 354:916-917
220.Perez D R, Lim W, Seiler J P, Yi G, Peiris M, Shortridge K F, Webster R G.Role of Quail in the interspecies transmission of H9 influenza A viruses: molecular changes on HA that correspond to adaptation from ducks to chickens.J Virol,2003, 77(5): 3148-3156
221.Pichlmair A,Schulz O,Tan C P,Naslund T LLiljestrom P, Weber F,Reise-Sousa C. RIG-I-mediated antiviral responses to single-stranded RNA bearing 5-prime-phosphates. Science, 2006, 314:997-1001
222.Price G E, Smith H,Sweet C.Differential induction of cytotoxicity and apop tosis by influenza virus strains of differing virulence.J General Virol, 1997,78: 2821-2829
223.Qian X Y, Alonso-Caplen F, Krug R M. Two functional domains of the influenza virus NS1 protein are required for regulation of nuclear export of mRNA.J Virol, 1994, 68(4):2433 - 24411
224.Qiu Y, Krug RM. The influenza virus NS1 protein is a poly(A)-binding protein that inhibits nuclear export of mRNAs containing poly(A).J Virol, 1994,68(4): 2425-2432
225.Qiu Y, Nemeroff M,Krug RM.The influenza virus NS1 protein binds to a specific region in human U6 SnRNA and inhibits U6-U2 and U6-U4 SnRNA interactions during splicing.RNA ,1995,1(3):304-316
226.Quinlivan M, Zamarin D, Garcia-Sastre A. Attenuation of equine influenza viruses through truncations of the NS1 protein. Virology, 2005, 79 (13): 8431-8439
227.Reinhardt J, Wolff T. The influenza A virus M 1 protein interacts with the cellular receptor of activated C kinase (RACK) 1 and can be phosphorylated by protein kinase C. Vet Microbiol, 2000,74(1-2): 87-100
228.Rigaut G, ShevchenkoA, Rutz B, WilmM, MannlM, SeraphinB. A generic protein purification method for protein complex characterization and proteome exploration. Nat Biotechnol, 1999,17(10): 1030-1032
229.Rimmelzwaan G F, van Riel D, Baars M, Bestebroer T M, van Amerongen G, Fouchier R A. Influenza A virus (H5N1) infection in cats causes systemic disease with potential novel routes of virus spread within and between hosts. Am J Pathol,2006, 168:176-83
230.Ronni T, Matikainen S, Sareneva T, Melen K, Pirhonen J, Keskinen P, Julkunen I. Regulation of IFN-α/β, MxA, 2-5-oligoadenylate synthetase and HLA gene expression in influenza A-infected human lung epithelial cells. J Immunol, 1997,158, 2363-2374
231.Saito T, Lim W, Suzuki T, Suzuki Y, Kida H, Nishimura S I, Tashiro M. Characterization of a human H9N2 influenza virus isolated in Hong Kong. Vaccine, 2001,209(1-2): 125-133
232.Schultz-Cherry S, Dybdahl-Sissoko N, Neumann G, Kawaoka Y, Hinshaw V S. Infuenza virus NS1 protein induces apoptosis in cultured cells. J Virol, 2001,75(17):7875-7881
233.Seo S H , Hoffmann E ,Webster RG. The NS1 gene of H5N1 influenza viruses circumvents the host antiviral cytokine responses. Virus Res,2004,103(122): 107-1131
234.Seo S H, Hoffmann E, Webster R G. Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nat Med, 2002, 8(9):950-9541
235.Serebriiskii I G, Fang R, Latypova E, Hopkins R, Vinson C, Joung J K, Golemis E A. A combined Yeast/Bacteria two-hybrid system: development and evaluation. Mol Cell Proteomics, 2005, 4(6): 819-826
236.Seth R B, Sun L,Ea C K,Chen Z J. Identification and Characterization of MAVS, a Mitochondrial Antiviral Signaling Protein that Activates NF-kappaB and IRF3.Cell, 2005,122:669-82
237.Seth R B,Sun L, Chen Z J.Antiviral innate immunity pathway. Cell Res,2006, 16: 141-147
238.Sha B, Luo M.Structure of a bifunctional membrane RNA binding protein, influenza virus matrix protein Ml. Nat Struct Biol, 1991,4 (3): 239-244
239.Shin Y K, Li Y, Liu Q, Anderson D H, Babiuk L A, Zhou Y. The influenza A virus NS1 protein activates the PI3K/Akt pathway to mediate anti-apoptotic signaling responses.J Virol,2007,81(7):3058-3067
240.Shin Y K, Liu Q, Tikoo S K, Babiuk L A, Zhou Y. Influenza A virus NS1 protein activates the Phosphatidylinositol 3-kinase (PI3K)/Akt pathway by direct interaction with the p85 subunit of PI3K. J Gen Virol, 2007, 88(Pt 1):13-18
241.Shinya K, Awakura T, Shimada A, Silvano F D, Umemura T, Otsuki K. Pathogenesis of pancreatic atrophies by avian influenza A virus infection .Avian Pathol, 1995, 24 :623-632
242.Shortridge K F, Zhou N N, Guan Y,Gao P, Ito T, Kawaoka Y,Kodihalli S, Krauss S, Markwell D, Murti KG, Norwood M, Senne D, Sims L, Takada A, Webster R G. Characterization of avian H5N1 influenza viruses from poultry in Hong Kong.Virology,1998,252:331-342
243.Shu Y, Yu H, Li D. Lethal Avian Influenza A (H5N1) infection in a pregnant woman in Anhui province China. New Engl J Med, 2006,354(13): 1421-1422
244.Sidhartha K, Biswas,Paul L. Influenza Virus Nucleoprotein Interacts with Influenza Virus Polymerase Proteins. Virology, 1998,8 :5493-5501
245.Smith E J, Marie I, Prakash A. IRF3 and IRF7 phosphorylation in virus-infected cells does not require double-stranded RNA-dependent protein kinase R or NF-kB kinase but is blocked by vaccinia virus E3L protein. J Biol Chem, 2001,276(12):8951-8957
246.Solorzano A,Webby R J, Lager K M, Janke B H,Garcia-Sastre A,Richt J A.Mutations in the NS1 protein of swine influenza virus impair anti-interferon activity and confer attenuation in pigs. J Virol, 2005, 79 (12): 7535-7543
247.Songserm T, Amonsin A, Jam-on R, Sae-Heng N, Meemak N, Pariyothorn N.Avian influenza H5N1 in naturally infected domestic cat. Emerg Infect Dis,2006,12:681-683
248.Stark G R, Ken I M, Williams B R G, Silverman R H, Schreiber R D. How cells respond to interferons. Ann Rev Biochem, 1998, 67,227-264
249.Sturm-Ramirez K M, Hulse-Post D J, Govorkova E A, Humberd J, Seiler P, Puthavathana P, Buranathai C, Nguyen T D, Chaisingh A, Long H T, Naipospos T S P, Chen H, Ellis T M,Guan Y, Peiris J S M, Webster R G. Are Ducks Contributing to the endemicity of highly pathogenic H5N1 influenza virus in asia? J Virol, 2005 79(17): 11269-11279
250.Suarea D L, Perdue M L. Multiple alignment comparison of the non-structural genes of influenza A viruses. Virus Res, 1998, 54 (1):59-69
251.Suarez D L.Evolution of avian influenza viruses. Vet Micro, 2000, 74: 15-27
252.Sun Q,Sun L, Liu H H.Chen X, Seth R B, Forman J, Chen Z J. The specific and essential role of MAVS in antiviral innate immune responses. Immunity ,2006,24: 633-642
253.Suzuki T, Takahashi T, GuoC T, Jwa Hidari K I P, MiyamotoD, GotoH, Kawaoka Y, SuzukiY.Sialidase activity of influenza A virus in an endocytic pathway enhances viral replication. J Virol ,2005,79(18) :11705-11715
254.SuzukiY, Ito T, Suzuki T, Miyamoto D, Hidari K I P J, Guo C T, Kida H, Webster G R , Chambers T M, Kawaoka Y.Sialyl sugar chains as receptors and determinants of host range of influenza A viruses. International Congress Serie,2001,1219 :521-525
255.Takaoka A, Hayakawa S, Yanai H, Stoiber D, Negishi H, Kikuchi H, Sasaki S, Imai K,Shibue T, Honda K, Taniguchi T. Integration of interferon-alpha/beta signalling to p53 responses in tumour suppression and antiviral defence. Nature,2003,424: 5162-523
256.Takeda K, Kaisho T, Akira S.Toll-like receptors. Annu Rev Immunol, 2003,21: 335-376
257.Takizawa T, Matsukawa S,Higuchi Y,Nakamura S, Nakanishi Y,Fukuda R.Induction of Programmed cell Death (apoptosis) by Influenza Virus Infection in Tissue Culture Cells. Gen Virol, 993,74 :2347-2355
258.Tamanna A, Asad U K. Identification of a casein kinase II phosphorylation domain in NS1 protein of H5N1 influenza virus. Bioinformation, 2007, 2(2): 57-61
259.Tan KM ,Chan S L,Tan K O,Yu V C.The Caenorhabditis elegans sex-determining protein FEM-2 and its human homologue, hFEM-2, are Ca2+/calmodulin-dependent protein kinase phosphatases that promote apoptosis. J Bio Chem, 2001, 276 (47): 44193-202
260.Thanawongnuwech R,Amonsin A, Tantilertcharoen R, Damrongwatanapokin S, Theamboonlers A, Payungporn S. Probable tiger-to-tiger transmission of avian influenza H5N1. Emerg Infect Dis, 2005, 5:699-701
261. Thomas A V, Palm M, BroersA D, Zezafoun H, Desmecht DJM. Genomic structure, organization and promoter analysis of the bovine (Bostaurus) Mxl gene. Gene,2004,26 :67-75
262.TorisuH,Kusuhara K, KiraR, BassunyW M, Sakai Y,Sanefuji M, Takemoto M, Hara T. Functional MxA promoter polymorphism associated with subacute sclerosing panencephalitis, Neurology, 2004,62 (3) :457-460
263.Treanor J J, Snyder M H, London W T, Murphy B R.The B allele of the NS gene of avian influenza viruses, but not the A allele, attenuates a human influenza A virus for squirrel monkeys. Virology, 1989,171 (1): 1-9
264.Turpin E,Luke K, Jones J, Tumpe y T, Konan K, Schultz-Cherry S. Influenza virus infection increases p53 activity: role of p53 in cell death and viral replication.J Virol, 2005,79:8802-8811
265.Ungchusak K, Auewarakul P,Dowell S F, Kitphati R, Auwanit W, Puthavathana P, Uiprasertkul M, Boonnak K, Pittayawonganon C,Cox N J, Zaki S R, Thawatsupha P, Chittaganpitch M, Khontong R, Simmerman J M, Chunsutthiwat S. Probable person-to-person transmission of avian influenza A (H5N1). N Engl J Med, 2005, 352(4) :333-340
266.Vattem, Krishna M, Staschke,Kirk A,Wek, Ronald C. Mechanism of activation of the double-stranded-RNA-dependent protein kinase,PKR. Eur J Biochem, 2001, 268: 3674-3684
267. Vey M, Orlich M, Adler S, Klenk H D, Rott R,Garten W. Hemagglutinin activation of pathogenic avian influenza viruses of serotype H7 requires the protease recognition motif R-X-K/R-R. Virology, 1992,188(1): 408-413
268.Vilcek J. Boosting p53 with interferon and viruses. Nat Immunol ,2003, 4: 825-826
269.Vines A, Wells K, Matrosovich M. The role of Influenza A virus hemagglutinin residues 226 and 228 in recep to r specificity and host range restriction. J Virol, 1998,72 (9): 7626-7631
270.Wang C B, Sun M, and Zhao T Z. Homology analysis of t he NS gene of H9N2 avian influenza virus isolates. Chinese J Prev Vet Med ,2004,26 (3): 177-180
271.Wang S, Shi W, Mweene A, Wei H, Bai G, Liu J H. Genetic analysis of the nonstructural (NS) genes of H9N2 chicken influenza viruses isolated in China during 1998-2002.Virus Gen, 2005,31(3):329-335
272.Wang X, Li M, Zheng H, Muster T, Palese P, Beg A A,Garcia-Sastre A. Influenza A virus NS1 protein prevents activation of NF-κB andinduction of alpha/beta interferon. J Virol,2000,74:11566-11573
273.Wang X, Li M, Zheng H, Muster T, Palese P, Beg A A, Garcia-SastreA. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J Virol, 2000,74,11566-11573
274.Washburn M P, Wolters D ,Yates J R.Large-scale analysis of the yeast proteome by multidimensional protein identification technology.Nat Biotech,2001,19(3):242-247
275.Wathelet M G,Lin C H, Parekh B S, Ronco L V,Howley P M, Maniatis T. Virus infection induces the assembly of coordinately activated transcription factors on the IFN-beta enhancer in vivo. Mol Cell, 1998,2:507-518
276.Weiss A, Littman U R. Signal transduction by lymphocyte antigen receptor. Cell, 1999,76:263-268
277.Williams B R C. Transcriptional regulation of interferon-stimulated genes. Eur Biochem, 1991,200(1):1-11
278.Wolff T, O'Neill R E, Palese P. NS1-binding protein (NS1-BP): a novel human protein that interacts with the influenza A virus nonstructural NS1 protein is delocalized in the nuclei of infected cells. J Virol, 1998,72(9):7170-7180
279.Wolff T.O'Neill R E, Palese P. Interaction cloning of NS1-I, a human protein that binds to the nonstructural NS1 proteins of influenza A and B viruses. J Virol, 1996, 70(8): 5363-5372
280.Wood G W, McCauley J W, Bashiruddin J B, Alexander D J.Deduced amino acid sequences at the haemagglutinin cleavage site of avian influenza A viruses of H5 and H7 subtypes. Arch Virol, 1993, 130 (1/2): 209-217
281.Wu Y, Voth GA. A computational study of the closed and open states of t he influenza A M2 proton channel. Biophys J, 2005, 88 (4) :2402-2411
282.Wurze r W J, Planz O, Ehrhardt C, Giner M, Silberzahn T, Pleschka S, Ludwig S. Caspase 3 activation is essential for efficient influenza virus propagation.EMBO J, 2003,22:2717-2728
283.Xu X Y, Subbarao K, Cox N J, Guo Y J. Evaluation of genetically modified reassortant H5N 1 influenza A virus vaccine candidate generated by plasmid based reverse genetics. Virology, 2003,305:192-200
284.YangY P, Huang C T, Huang X P, Pardoll D M.Persistent Toll-like receptor signals are required for reversal of regulatory T cell-mediated CD8 tolerance. Nat Immunol, 2004,5 (5): 508-515
285.Yoneyama M, Kikuchi M, Matsumoto K, Imaizumi T, Miyagishi M, Taira K. Foy E. Loo Y M. Gale M Jr, Akira, S.Yonehara S, Kato A. Fujita T. Shared and Unique Functions of the DExD/H-Box Helicases RIG-I, MDA5, and LGP2 in Antiviral Innate Immunity. J Immunol, 2005, 175: 2851-2858
286.Yoneyama M,Kikuchi M,Natsukawa T,Sbinobu N,Imaizumi T,Miya-gishi M. The RNA helicase RIG-1 has an essential function in double-stranded RNA-induced innate antiviral responses. Nat Immunol ,2004,5:730-737
287.Yu Q, Konig R, Pillai S, Chiles K. Single-strand specificity of APOBEC3G accounts forminus-strand deamination of the H IV genome. Nat Struct Mol Biol, 2004,11 (5): 435-442
288.Yuichi W, Akiko S,Kazufumi S, Takenori T ,Yoshinobu N.Stimulation of phagocytosis of influenza virus infected cells through surface desialylation of macrophages by viral neuraminidase. Microbiol Immunol, 2004, 48 (11):875-881
289.Zhirnov O P, Klenk H D. Control of apoptosis in influenza virus-infected cells by up-regulation of Akt and p53 signaling Apoptosis,,2007, 12:1419-1432
290.Zhirnov P, Konakova T E, Wolff T, Klenk H D.NS1 protein of influenza A virus down regulates apoptosis. J Virol, 2002,76(4):1617-1625
291.Zhu H, Bilgin M, Bangham R, Hall D, Casamayor A, Bertone P,Lan N, Jansen R, Bidlingmaier S, Houfek T,Mitchell T, Miller P, Dean RA, Gerstein M, Snyder M. Global analysis of protein activities using proteome chips. Science, 2001,293(5537): 2101-2105