两株H5N1亚型禽流感病毒对SPF鸭的致病性研究
|
摘要
本试验利用2株1996年和2004年从我国广东地区分离的H5N1亚型禽流感病毒感染4周龄SPF鸭,针对H5N1亚型禽流感病毒对SPF鸭的致病性进行了系统研究。以10~6 EID_50的病毒量鼻腔感染SPF鸭后,于第3、5、7、9 d分别剖杀感染鸭3只,采集喉头拭子、泄殖腔拭子、各组织脏器,进行病毒含量滴定、荧光定量PCR检测、病理组织学和免疫组织化学检验,探讨了H5N1亚型禽流感病毒在鸭体内各脏器的含量、分布、引起的病理变化以及排毒情况。
2株禽流感病毒对鸭表现为不同的致病性:GS/GD/1/96毒株对SPF鸭的致死率为0,且无临床症状,剖检后无肉眼可见病理变化,各器官均分离不到病毒,免疫组织化学检测未发现病毒抗原信号;而DK/GDJD/23/04毒株对SPF鸭的致死率为100%,且表现典型的神经症状,剖检可见脑膜点状出血,胸腺出血,脾脏肿大并有坏死灶,肺脏严重充血、出血,腺胃粘膜弥散性出血。病理组织学检查发现全身各脏器以出血、充血、细胞变性坏死和炎性细胞浸润为主要特征的病理变化。各器官均可分离到病毒,脑组织病毒含量最高,免疫组织化学检测发现有病毒抗原信号。
应用ELISA、细胞培养技术及CCK测定法,对4周龄SPF鸭感染H5N1 AIV后,其血清中IL-2、IFN-γ的含量,脾脏淋巴细胞对ConA刺激的T淋巴细胞增殖功能动态变化的研究发现,GS/GD/1/96毒株可促使外周血淋巴细胞分泌和释放IL-2和IFN-γ(p＜0.05),但不能引起外周血T淋巴细胞的转化率的变化;而DK/GDJD/23/04毒株不仅可促使外周血淋巴细胞合成和释:IL-2(p＜0.05)和IFN-γ(p＜0.01),最主要的是能引起外周血T淋巴细胞的转化率显著降低(P＜0.01),并引起脾、胸腺及盲肠扁桃体的出血和淋巴细胞减少的变化,说明该病毒具有显著的抑制鸭细胞免疫功能的作用。进一步证实了DK/GDJD/23/04毒株感染后可引起鸭免疫功能抑制。
全基因组测序分析表明,2株病毒均为高致病性毒株,在分子结构上,二者HA蛋白上的糖基化位点完全一致,二者HA蛋白的差异有2处,一是DK/GDJD/23/04裂解位点为连续的5个碱性氨基酸(-RRRKK-),GSGD/1/96为6个连续的碱性氨基酸(-RRRKKR-);二是在可能的受体结合位点224-229位,DK/GDJD/23/04的氨基酸为RLVPKI,而GSGD/1/96的序列为RLVPEI,即228位氨基酸E到K的变化。二者NA蛋白的差异有2处,一是DK/GDJD/23/04在NA蛋白颈部49-68位缺20个氨基酸,相应的缺失了4个潜在糖基化位点。GSGD/1/96 NA蛋白颈部没有发生缺失。二是DK/GDJD/23/04NA蛋白在386位有糖基化位点,而GSGD/1/96 NA蛋白在386位没有糖基化位点。DK/GDJD/23/04的NA蛋白颈部49-68位20个氨基酸缺失、NS1蛋白在80-84位有5个氨基酸缺失,这些缺失存在于大多数H5N1亚型人源和禽源分离株中,有利于禽流感病毒在家禽中传播,成为2002-2004年流行的优势病毒。上述这些差异可能是2株病毒对鸭致病性差异的重要原因。遗传演化分析表明,二株病毒存在差异,DK/GDJD/23/04与04年及以后的流行株亲缘关系很近,此毒株已在家禽中传播并发生了变异。
To assess the pathogenicity of influenza A virus in ducks,two viruses A/goose/Guangdong/1/96(H5N1)(GS/GD/1/96) and A/duck/GuangdongJiedong/23/2004(H5N1)(DK/GDJD/23/04) isolated from Guangdong province were selected in the study,20 SPF ducks with 4 weeks old in each group were inoculated nasally with 10~6 EID_(50) to evaluate the pathogenicity of two viruses.The content of virues,the distribution of virues and the pathological changes in multiorgans in SPF ducks were caused by the H5N1 subtype avian influenza virus,so the virus titration of multiorgans and swabs,the real time PCR,and also pathological and immunochemistry analysis at different time point were done.
All ducks survived post infection(p.i.) with GS/GD/1/96 and didn't show any clinical signs,no virus was detected from the organs on days p.i,whereas DK/GDJD/23/04 caused 100%mortality in the ducks,furthermore,DK/GDJD/23/04 caused ducks with severe neurological dysfunction,viruses were re-isolated from many tissues.Histological lesions were observed in multiple parenchyma organs and were characterized by congestion, hemorrhage,degeneration to necrosis or'heterophilis infliltration.This virus could replicate very well in the brains,and the titers reach to the highest.
In this study,Enzyme-Linked ImmunoSorbent Assay(ELISA),CCK assay were used to research the dynamic changes of the content of IL-2,IFN_(-γ) in serum and T lymphocytes to ConA in spleen of 4-week-old duck infected with AⅣ.The content of IL-2,IFN_(-γ) in serum were increased compared with control groups and statistically significant(p＜0.05), But the proliferative function of T lymphocytes to ConA in spleen of 4-week-old ducks infected with GS/GD/1/96 were no significant different(p＞0.05).The content of IL-2,IFN_(-γ) in serum were increased compared with control groups and statistically significant(p＜0.05,p＜0.01),But the proliferative function of T lymphocytes to ConA in spleen of 4-week-old ducks infected with DK/GDJD/23/04 were decreased compared with control ducks and statistically significant(p＜0.01).The results showed that cellular immune in ducks infected with DK/GDJD/23/04 was critically inhibited,which is the primary element in immune subordinate ducks.
Genome sequencing and analysis showed that the two viruses are highly pathogenic strains,in the molecular structure,both the HA protein glycosylation sites exactly the same, the difference between the two HA protein has two:first,DK/GDJD/23/04 is the cleavage site for the five consecutive basic amino acids(-RRRKK-),GSGD/1/96 for six consecutive basic amino acids(-RRRKKR-),Second,Receptor binding sites of 224-229 have changed. The amino acids of DK/GDJD/23/04 HA protein for RLVPKI and the sequence of GSGD/1/96 HA protein for RLVPEI,which has E to K changed in 228 amino acid site.The difference between the two NA proteins have two:first,DK/GDJD/23/04 has a 20-amino acid delection in NA stalk(residues49-68),the corresponding loss of the four potential glycosylation sites.There was no delection in NA stalk in GSGD/1/96.The second is DK/GDJD/23/04 NA protein in the 386 has a potential glycosylation site,and GSGD/1/96 NA protein in the 386 did not have.A 20-amino acid delection in NA stalk(residues49-68)and a 5-amino acid delection in NS1 stalk(residues80-84)which were in the most of influenza A viruses have been the co-genetic marker of the majority isolates circulating during recent years.Phylogenetic analysis revealed that both HA and NA genes of DK/GDJD/23/04 had genetically close relationship with DK/China/E319-2/03,which suggested that they came from the same origin.
2株禽流感病毒对鸭表现为不同的致病性:GS/GD/1/96毒株对SPF鸭的致死率为0,且无临床症状,剖检后无肉眼可见病理变化,各器官均分离不到病毒,免疫组织化学检测未发现病毒抗原信号;而DK/GDJD/23/04毒株对SPF鸭的致死率为100%,且表现典型的神经症状,剖检可见脑膜点状出血,胸腺出血,脾脏肿大并有坏死灶,肺脏严重充血、出血,腺胃粘膜弥散性出血。病理组织学检查发现全身各脏器以出血、充血、细胞变性坏死和炎性细胞浸润为主要特征的病理变化。各器官均可分离到病毒,脑组织病毒含量最高,免疫组织化学检测发现有病毒抗原信号。
应用ELISA、细胞培养技术及CCK测定法,对4周龄SPF鸭感染H5N1 AIV后,其血清中IL-2、IFN-γ的含量,脾脏淋巴细胞对ConA刺激的T淋巴细胞增殖功能动态变化的研究发现,GS/GD/1/96毒株可促使外周血淋巴细胞分泌和释放IL-2和IFN-γ(p＜0.05),但不能引起外周血T淋巴细胞的转化率的变化;而DK/GDJD/23/04毒株不仅可促使外周血淋巴细胞合成和释:IL-2(p＜0.05)和IFN-γ(p＜0.01),最主要的是能引起外周血T淋巴细胞的转化率显著降低(P＜0.01),并引起脾、胸腺及盲肠扁桃体的出血和淋巴细胞减少的变化,说明该病毒具有显著的抑制鸭细胞免疫功能的作用。进一步证实了DK/GDJD/23/04毒株感染后可引起鸭免疫功能抑制。
全基因组测序分析表明,2株病毒均为高致病性毒株,在分子结构上,二者HA蛋白上的糖基化位点完全一致,二者HA蛋白的差异有2处,一是DK/GDJD/23/04裂解位点为连续的5个碱性氨基酸(-RRRKK-),GSGD/1/96为6个连续的碱性氨基酸(-RRRKKR-);二是在可能的受体结合位点224-229位,DK/GDJD/23/04的氨基酸为RLVPKI,而GSGD/1/96的序列为RLVPEI,即228位氨基酸E到K的变化。二者NA蛋白的差异有2处,一是DK/GDJD/23/04在NA蛋白颈部49-68位缺20个氨基酸,相应的缺失了4个潜在糖基化位点。GSGD/1/96 NA蛋白颈部没有发生缺失。二是DK/GDJD/23/04NA蛋白在386位有糖基化位点,而GSGD/1/96 NA蛋白在386位没有糖基化位点。DK/GDJD/23/04的NA蛋白颈部49-68位20个氨基酸缺失、NS1蛋白在80-84位有5个氨基酸缺失,这些缺失存在于大多数H5N1亚型人源和禽源分离株中,有利于禽流感病毒在家禽中传播,成为2002-2004年流行的优势病毒。上述这些差异可能是2株病毒对鸭致病性差异的重要原因。遗传演化分析表明,二株病毒存在差异,DK/GDJD/23/04与04年及以后的流行株亲缘关系很近,此毒株已在家禽中传播并发生了变异。
To assess the pathogenicity of influenza A virus in ducks,two viruses A/goose/Guangdong/1/96(H5N1)(GS/GD/1/96) and A/duck/GuangdongJiedong/23/2004(H5N1)(DK/GDJD/23/04) isolated from Guangdong province were selected in the study,20 SPF ducks with 4 weeks old in each group were inoculated nasally with 10~6 EID_(50) to evaluate the pathogenicity of two viruses.The content of virues,the distribution of virues and the pathological changes in multiorgans in SPF ducks were caused by the H5N1 subtype avian influenza virus,so the virus titration of multiorgans and swabs,the real time PCR,and also pathological and immunochemistry analysis at different time point were done.
All ducks survived post infection(p.i.) with GS/GD/1/96 and didn't show any clinical signs,no virus was detected from the organs on days p.i,whereas DK/GDJD/23/04 caused 100%mortality in the ducks,furthermore,DK/GDJD/23/04 caused ducks with severe neurological dysfunction,viruses were re-isolated from many tissues.Histological lesions were observed in multiple parenchyma organs and were characterized by congestion, hemorrhage,degeneration to necrosis or'heterophilis infliltration.This virus could replicate very well in the brains,and the titers reach to the highest.
In this study,Enzyme-Linked ImmunoSorbent Assay(ELISA),CCK assay were used to research the dynamic changes of the content of IL-2,IFN_(-γ) in serum and T lymphocytes to ConA in spleen of 4-week-old duck infected with AⅣ.The content of IL-2,IFN_(-γ) in serum were increased compared with control groups and statistically significant(p＜0.05), But the proliferative function of T lymphocytes to ConA in spleen of 4-week-old ducks infected with GS/GD/1/96 were no significant different(p＞0.05).The content of IL-2,IFN_(-γ) in serum were increased compared with control groups and statistically significant(p＜0.05,p＜0.01),But the proliferative function of T lymphocytes to ConA in spleen of 4-week-old ducks infected with DK/GDJD/23/04 were decreased compared with control ducks and statistically significant(p＜0.01).The results showed that cellular immune in ducks infected with DK/GDJD/23/04 was critically inhibited,which is the primary element in immune subordinate ducks.
Genome sequencing and analysis showed that the two viruses are highly pathogenic strains,in the molecular structure,both the HA protein glycosylation sites exactly the same, the difference between the two HA protein has two:first,DK/GDJD/23/04 is the cleavage site for the five consecutive basic amino acids(-RRRKK-),GSGD/1/96 for six consecutive basic amino acids(-RRRKKR-),Second,Receptor binding sites of 224-229 have changed. The amino acids of DK/GDJD/23/04 HA protein for RLVPKI and the sequence of GSGD/1/96 HA protein for RLVPEI,which has E to K changed in 228 amino acid site.The difference between the two NA proteins have two:first,DK/GDJD/23/04 has a 20-amino acid delection in NA stalk(residues49-68),the corresponding loss of the four potential glycosylation sites.There was no delection in NA stalk in GSGD/1/96.The second is DK/GDJD/23/04 NA protein in the 386 has a potential glycosylation site,and GSGD/1/96 NA protein in the 386 did not have.A 20-amino acid delection in NA stalk(residues49-68)and a 5-amino acid delection in NS1 stalk(residues80-84)which were in the most of influenza A viruses have been the co-genetic marker of the majority isolates circulating during recent years.Phylogenetic analysis revealed that both HA and NA genes of DK/GDJD/23/04 had genetically close relationship with DK/China/E319-2/03,which suggested that they came from the same origin.
引文
1. Ali, A., R. T. Avalos, E. Ponimaskin, and D. P. Nayak. Influenza virus assembly: effect of influenza virus glycoproteins on the membrane association of Ml protein. J Virol. 2000. 74:8709-19.
2. Almond, J. W. A single gene determines the host range of influenza viruses. Nature. 1977. 270: 617-618.
3. Avalos R. T., Z. Yu, and D. P. Nayak. Association of influenza virus NP and Ml proteins with cellular cytoskeletal elements in influenza virus-infected cells. J Virol. 1997.71(4):2947-58
4. Baigent, S. J., R. C. Bethell, and J. W. McCauley. Genetic analysis reveals that both haemagglutinin and neuraminidase determine the sensitivity of naturally occurring avian influenza viruses to zanamivir in vitro. Virology 1999.263: 323-338.
5. Baigent, S.J., and J. W. McCauley. Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture. Virus Res 2001.79: 177-185.
6. Banks, J., Speidel E. C., McCauley J. W., and Alexander D. J.. Phylogenetic analysis of H7 haemagglutinin subtype influenza A viruses. Arch Virol 2000. 145: 1047-1058.
7. Baum,L. G., and J. C. Paulson. The N2 neuraminidase of human influenza viruses has acquired a substrate specificity complimentary to the haemagglutinin receptor specificity. Virology 1991.180: 10-15.
8. Bazzigher, L., A. Schwarz, and P. Staeheli. No enhanced influenza virus resistance of murine and avian cells expressing cloned duck Mx protein. Virology 1993.195: 100-112.
9. Beaton, A. R., and R. M. Krug. Transcription antitermination during influenza viral template RNA synthesis requires the nucleocapsid protein and the absence of a 5' capped end. Proc. Natl. Acad. Sci. USA 1986. 83:6282-6286.
10. Bennink, J. R., J. W. Yewdell, G. L. Smith, and B. Moss. Anti-influenza virus cytotoxic T lymphocytes recognize the three viral polymerases and a nonstructural protein: responsiveness to individual viral antigens is major histocompatibility complex controlled. J Virol 1987.61: 1098-1102.
11. Biswas S. K., P. L. Boutz, D.P. Nayak. Influenza virus nucleoprotein interacts with influenza virus polymerase proteins. J Virol. 1998.72:5493-5501.
12. Blok, J., and G. M. Air. Variation in the membrane-insertion and 'stalk' sequences in eight sub-types of influenza type A virus neuraminidase. Biochem 1982. 21: 4001-4007.
13. Brown CC, Olander HJ, Senne DA. A pathogenesis study of highly pathogenic avian influenza virus H5N2 in chickens, using immunohistochemistry. J Comp Pathol. 1992. 107(3):341-8.
14. Bui, M., G. Whittaker, and A. Helenius. Effect of Ml protein and low pH on nuclear transport of influenza virus ribonucleoproteins. J. Virol. 1996. 70:8391-8401.
15. Bukrinskaya, A. G., N. K. Vorkunova, G. V. Kornilayeva, R. A. Narmanbetova, and G. K..Bullido R, Gomez-Puertas P, Saiz MJ, Portela A. Influenza A virus NEP (NS2 protein) downregulates RNA synthesis of model template RNAs. J Virol. 2001. 75:4912-7.
16. Capua I, Mutinelli F. Mortality in Muscovy ducks (Cairina moschata) and domestic geese (Anser anser var. domesticus) associated with natural infection with a highly pathogenic avian influenza virus ofH7N1 subtype. Avian Pathology, 2001. 30: 179-183.
17. Castrucci, M. R., and Y. Kawaoka. Biologic importance of neuraminidase stalk length in influenza A virus. J Virol 1993. 67: 759-764.
18. Chen H., Deng G., Li Z., et al. The evolution of H5N1 influenza viruses in ducks in southern China. Proceedings of the National Academy of Sciences, U.S.A,2004.101(28), 10452-10457.
19. Chen, Z., Y. Li, and R. M. Krug. Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery. EMBO J. 1999.18:2273-2283
20. Cheung, C. Y., L. L. M. Poon, A. S. Lau, W. Luk, Y. L. Lau, K. F. Shortridge, S. Gordon, Y. Guan, J. S. M. Peiris. Induction of pro-inflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet 2002.360: 1831-1837.
21. Chizhmakov, I. V., F. M. Geraghty, D. C. Ogden, A. Hayhurst, M. Antoniou, and A. J. Hay. Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells. J. Physiol. 1996.494:329-336.
22. Ciampor, F., C.A.Thompson, S. Grambas, and A. J.Hay. Regulation of pH by the M2 protein of influenza A viruses. Virus Res. 1992a. 22:247-258.
23. Ciampor, F., P. M. Bayley, M. V. Nermut, E. M. Hirst, R. J. Sugrue, and A. J. Hay. Evidence that the amantadine-induced, M2-mediated conversion of influenza A virus hemagglutinin to the low pH conformation occurs in an acidic trans Golgi compartment. Virology1992b. 188:14-24.
24. Claas, E., A. Osterhaus, R. van Beek, J. De Jong, , G. Rimmelzwaan, D. Senne, S. Krauss, K. Shortridge, and R. G Webster. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 1998.351, 472-477.
25. Compans, R. W., and P. W. Choppin. 1975. Reproduction of myxoviruses, p. 179-252. In H. Fraenkel-Conrat, and R. R. Wagner (ed.), Comprehensive virology, vol. IV. Plenum Press, New York, N.Y.
26. Connor, R. J., Y. Kawaoka, R. G Webster, J. C. Paulson. Receptor specificity in human, avian and equine H2 and H3 influenza virus isolates. Virology 1994.205:17-23.
27. Criswell BS, Couch RB, Greenberg SB, Kimzey SL.The lymphocyte response to influenza in humans. Am Rev Respir Dis. 1979;120(3):700-4.
28. David L Suarez. Evolution of avian influenza viruses. Vet.Microbiol, 2003, 74:15- 27.
29. de la Luna, S., P. Fortes, A. Beloso, and J. Ortin. Influenza virus NS 1 protein enhances the rate of translation initiation of viral mRNAs. J. Virol. 1995.69:2427-2433.
30. Deborah MB, Eulogia R, Susan L. Swain CD4 T cell responses to influenza infection. Immunol . 2004. (16):171-177
31. Denis F, Alain S, Hantz S, et al. 2005. Antiviral vaccination and respiratory mucosal immunity: still disappointing results from a seductive idea.Press Med .34(17): 1245-1253
32. Dennis JA. How dangerous are avian influenza viruses for humans? [J].world poultry,2002,Special,l 1-12.
33. Desphande, K. L., V. A. Fried, M. Ando, and R. G. Webster. Glycosylation affects cleavage of an H5N2 influenza virus hemagglutinin and regulates virulence. Proc. Natl. Acad. Sci. USA 1987.84:36-40.
34. Eichelberger, M., W. Allan, M. Zijlstra, R. Jaenisch, and P. C. Doherty. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8~+ T cells. J Exp Med 1991. 174: 875-880.
35. Els, M. C., G. M. Air, K. G. Murti, R. G. Webster, and W. G. Laver. An 18-amino acid deletion in an influenza neuraminidase. Virology 1985. 142: 241-247.
36. Enami, K., T. A. Sato, S. Nakada, and M. Enami. Influenza virus NS1 protein stimulates translation of the M1 protein. J. Virol. 1994.68:1432-1437.
37. Fortes, P., A. Beloso, and J. Ortin. Influenza virus NS1 protein inhibits pre-mRNA splicing and bloDKs mRNA nucleocytoplasmic transport. EMBO J. 1994. 13:704-712.
38. Galarza J. M., A . Sowa, V. M. Hill, R. Skorko, and D.F. Summers. Influenza A virus NP protein expressed in insect cells by a recombinant baculovirus is associated with a protein kinase activity and possesses single-stranded RNA binding activity. Virus Res. 1992.24:91-106.
39. Garcia-Sastre, A., A. Egorov, D. Matassov, S. Brandt, D. E. Levy, J. E. Durbin, P. Palese, and T. Muster. Influenza A virus laDKing the NS1 gene replicates in interferon-deficient systems. Virology 1998.252:324-330.
40. Garten, W., and H.-D. Klenk. Understanding influenza virus pathogenicity. Trends Microbiol. 1999.7:99-100.
41. Goto, H., K. Wells, A. Takada, and Y. Kawaoka. Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus. J Virol 2001. 75: 9297-9301.
42. Grambas, S., and A. J. Hay. Maturation of influenza A virus hemagglutinin-estimates of the pH encountered during transport and its regulation by the M2 protein. Virology. 1992a. 190:11 -18.
43. Grambas, S., M. S. Bennett, and A. J. Hay. Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses. Virology. 1992b. 191:541-549.
44. Grey H M.Duck immunoglobulins I structural studies on a 5.7S and 7.8S g-globulin. J Immunol,1967,98:811-819.
45. Guo L, Lu X, Kang S M ,et al Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles. Virology,2003,313(2)1502-513.
46. Hatta, M., P. Gao, P. Halfmann, and Y. Kawaoka. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001.293: 1840-1842.
47. Hay, A. J., B. Lomniczi, A. R. Bellamy, and J. J. Skehel. 1977. Transcription of the influenza virus genome. Virology 83:337-355.
48. Higgins D A,Shortridge K F,Ng PLK.Bile immunoglobulin of the duck (Anas platyrhynchos).II.Antibody response in influenza A virus infections. Immunology. 1987,62 :499-504.
49. Hinshaw VS, Webster RG, Naeve CW, Murphy BR. Altered tissue tropism of human-avian reassortant influenza viruses Virology. 1983 Jul 15;128(1):260-3.
50. Holsinger, L. J., D. Nichani, L. H. Pinto, and R. A. Lamb. Influenza A virus M2 ion channel protein: a structure-function analysis. J. Virol. 1994.68:1551-1563.
51. Holt, P S. Enhancement of chicken lymphocyte activation and lymphokine release by avian influenza virus. Dev Comp Immunol,1990.14:447-455.
52. Holt, P S, Larimer J M. Stimulatory effect Of avian influenza virus on chicken lymphocyte.Avian Dis,1989.33:743-749.
53. Homme, P J, Easterday B C. Avian influenza virus infections.IV.Response of pheasants,duck,and geese to influenza A-turkey-Wisconsin-1966 virus. Avian Dis. 1970.14,285-290.
54. Hooper PT, Russell GW, Selleck PW, Stanislawek WL.Observations on the relationship in chickens between the virulence of some avian influenza viruses and their pathogenicity for various organs.Avian Dis. 1995 Jul-Sep;39(3):458-64.
55. Horimoto, Y., Y. Yamazaki, T. Fukushima, T. Saito, S. E. Lindstrom, K. Omoe, R. Nerome, W. Lim, S. Sugita, and K. Nerome. Evolutionary characterization of the six internal genes of H5N1 human influenza A virus. J. Gen. Virol. 2000. 81:1293-1303.
56. Hughson, F.M.. Structural characterization of viral fusion proteins. Curr. Biol. 19955:265-274.
57. Hulse DJ., Webster RG, Russell RJ, Perez DR. Molecular determinants within the surface proteins involved in the pathogenicity of H5N1 influenza viruses in chickens. J Virol.2004. 78(18):9954-64.
58. Inkster, M. D., V. S. Hinshaw, and I. T. Schulze. The haemagglutinins of duck and human H1 influenza viruses differ in sequence conservation and in glycosylation. J Virol 1993.67: 7436-7443.
59. Kawaoka Y., C. W. Naeve, R. G. Webster. Is virulence of H5N2 influenza viruses in Chickens associated with loss of carbohydrate from the hemagglutinin? Virology. 1984. 139:303-16.
60. Kawaoka, Y., and R. G. Webster. Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. Proc. Natl.Acad. Sci. USA 1988. 85:324-328.
61. Kawaoka, Y, O. T. Gorman, T. Ito, K. Wells, R. O. Donis, M. R. Castrucci, I. Donatelli, R. G. Webster. Influence of host species on the evolution of the nonstructural (NS) gene of influenza A viruses. Virus Res 1998: 55: 143-156.
62. Kawaoka, Y., S. Krauss, R. G. Webster. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol 1989.63: 4603-4608.
63. Kida H, Ito T, Yasuda J, et al, Potential for transmission of avian influenza viruses to pigs. J Gen Virol 1994, 75: 2183-2188.
64. Klenk, H.D., R. Rott, M. Orlich, and J. Blodorn. Activation of influenza A viruses by trypsin treatment. Virology 1975.68:426-439.
65. Ko, J.H., H.K. Jin, A. Asano, A. Takada, A. Ninomiya, H. Kida, H. Hokiyama, M. Ohara, M. Tsuzuki, M. Nishibori, M. Mitzutani, and T. Watanabe. Polymorphisms and the differential antiviral activity of the chicken Mx gene. Genome Res. 2002.12:595-601.
66. Kobasa, D., K. Wells, and Y. Kawaoka. Amino acids responsible for the absolute sialidase activity of the influenza A virus neuraminidase: relationship to growth in the duck intestine. J Virol 2001.75: 11773-11780.
67. Kobasa, D., S. Kodihalli, M. Luo, M. R. Castrucci, I. Donatelli, T. Suzuki, and Y. Kawaoka. Amino acid residues contributing to the substrate specificity of the influenza A neuraminidase. J Virol. 1999.73:6743-6751.
68. Krug, R. M. Priming of influenza viral RNA transcription by capped heterologous RNAs. Curr. Top. Microbiol. Immunol. 1981.93:125-149.
69. Krug, R. M., F. V. Alonso-Caplen, I. Julkunem, and M. G. Katze. Expression and replication of the influenza virus genome, p. 89-152. In R. M. Krug (ed.), The influenza viruses. Plenum Press, 1989.New York, N.Y.
70. Lamb, R. A., and R. M. Krug. Orthomyxoviridae: the viruses and their replication, p. 1353-1395. In B. N. Fields, D. M. Knipe, and P. M. Howley (ed.), 1996. Fields virology, 3rd ed. Lippincott-Raven, Philadelphia, Pa.
71. Laudert E, Sivaanandan V,Halvorson D.Effect of an H5N1 avian influenza virus infection on the immune system of mallard ducks. Avian Dis.1993. 37: 845-853.
72. Li Ze jun. Molecular basis of replication of Duck H5N1 influenza viruses in a mammalian model. Virol, 2005, 79(18): 12058-12064.
73. Li, S., M. Xu, and K. Coelingh. Electroporation of influenza virus ribonucleoprotein complexes for rescue of the nucleoprotein and matrix genes. Virus Res. 1995. 37:153-161.
74. Liang B, Hyland L, Hou S.Nasal-associated lymphoid tissue is a site of long-term virus-specific antibody production following respiratory virus infection of mice. J Virol. 2001 ;75(11):5416-20.
75. Lohmeyer, J., L. T. Talens, and H. D. Klenk. Biosynthesis of the influenza virus envelope in abortive infection. J. Gen. Virol. 1979.42:73-88.
76. Lu, Y., M. Wambach, M. G. Katze, and R. M. Krug. Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylated the eIF-2 translation initiation factor. Virology 1995.214: 222-228.
77. Lu, Y., X. Y. Qian, and R. M. Krug. The influenza virus NS1 protein: a novel inhibitor of pre-mRNA splicing. Genes Dev. 1994.8:1817-1828.
78. Ludwig, S., X. Wang, C. Ehrhardt, H. Zheng, N. Donelan, O. Planz, S. Pleschka, A. Garcia-Sastre, G. Heins, and T. Wolff. The influenza A virus NS 1 protein inhibits activation of Jun N-terminal kinase and AP-1 transcription factors. J Virol 2002.76: 11166-11171.
79. Martin, K., and A. Helenius. Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import. Cell 1991.67:117-130.
80. Massin P, van der Werf S, Naffakh N, Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. J Virol. 2001;75(11):5398-404.
81. Matrosovich, M., N. Tuzikov, A. Bovin, A. Gambaryan, A. Klimov, M.R. Castrucci, I. Donatelli, and Y. Kawaoka. Early alterations of the receptor-binding properties of H1, H2, H3 avian influenza virus haemagglutinins after their introduction into mammals. J Virol 2000.74: 8502-8512.
82. Matsuo K, Iwasaki T, Asanuma H, Yoshikawa T, Chen Z, Tsujimoto H, Kurata T, Tamura SS. Cytokine mRNAs in the nasal-associated lymphoid tissue during influenza virus infection and nasal vaccination. Vaccine. 2000 Jan 31;18(14):1344-50.
83. Murphy, B. R., and R. G. Webster. Orthomyxoviruses, p. 1397-1445. In B. N. Fields, D. M. Knipe, and P. M. Howley (ed.), 1996.Fields virology, 3rd ed. Lippincott-Raven, Philadelphia, Pa.
84. Naffakh, N., P. Massin, N. Escriou, B. Crescenzo-Chaigne, and S. van der Werf. Genetic analysis of the compatibility between olymerase proteins from humans and avian strains of influenza A viruses. J. Gen. Virol. 2000. 81:1283-1291.
85. Neumann G, Hughes MT, Kawaoka Y. Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1. EMBO J. 2000. 19:6751-8.
86. Neumann, G, M. R. Castrucci, and Y. Kawaoka. Nuclear import and export of influenza virus nucleoprotein. J. Virol. 1997.71:9690-9700.
87. Nobusawa, E., T. Aoyama, H. Kato, Y. Suzuki, Y. Tateno, and K. Nakajima. Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of haemagglutinins of influenza A viruses. Virology 1991.182:475-485.
88. Odagiri T, Tobita K. Mutation in NS2, a nonstructural protein of influenza A virus, extragenically causes aberrant replication and expression of the PA gene and leads to generation of defective interfering particles. Proc Natl Acad Sci U S A. 1990. 87:5988-92.
89. Ohuchi, M., A. Cramer, M. Vey, R. Ohuchi, W. Garten, and H.-D. Klenk. Rescue of vector-expressed fowl plague virus hemagglutinin in biologically active form by acidotropic agents and coexpressed M2 protein. J. Virol. 1994.68:920-926.
90. Ohuchi, M., R. Ohuchi, A. Feldmann, and H. K. Klenk. Regulation of receptor binding affinity of influenza virus haemagglutinin by its carbohydrate moiety. J Virol 1997.71:8377-8384.
91. Okazaki, K., Y. Kawaoka, R. G. Webster. Evolutionary pathways of the PA genes of influenza A viruses. Virology 1989.172: 601-608.
92. O'Neill, E., S. L. Krauss, J. M. Riberdy, R. G Webster, and D. L. Woodland. Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice. J Gen Virol 2000.81: 2689-2696.
93. O'Neill, R. E., J. Talon, and P. Palese. The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J. 1998. 17:288-296.
94. Park, Y. W., and M. G Katze. Translational control by influenza virus. Identification of cis-acting sequences and trans-acting factors which may regulate selective viral mRNA translation. J. Biol. Chem. 1995.270:28433-28439
95. Pensaert MK. Evidence for the natural transmission of influenza A virus from wild ducks to swine and itspotential importance for mam.Bull WHO ,1981,59:75-77.
96. Perdue, M. L., J. W. Latimer, and J. M. Crawford. A novel carbohydrate addition site of the haemagglutinin protein of a highly pathogenic H7 subtype avian influenza virus. Virology 1995. 213: 276-281.
97. Perkins L E, Swayne D E. Susceptibility of laughing gulls to H5N1 and H5N3 high pathogenic avian influenza viruses[J]. Avian Disease,2002, 46: 877-885.
98. Pilaipan P A, Prasert C C, Pakapak S,et al.Molecular Characterization of the Complete Genome of Human Influenza H5N1 Virus Isolates from Thailand [J].JGen Vi rol,2005,86:4232433.
99. Pinto, L. H., L. J. Holsinger, and R. A. Lamb. Influenza virus M2 protein has ion channel activity. Cell 1992.69:517-528.
100. Plotch, S. J., M. Bouley, and R. M. Krug. Transfer of 5'-terminal cap of globin mRNA to influenza viral complementary RNA during transcription in vitro. Proc Natl Acad Scr USA 1979.76:1618-1622.
101. Qiu, Y., and R. M. Krug. The influenza virus NS1 protein is a poly(A)-binding protein that inhibits nuclear export of mRNAs containing poly(A). J. Virol. 1994. 68:2425-2432
102. Qiu, Y, M. Nemeroff, and R. M. Krug. 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 1995.1:304-316.
103. Reed L J, Muench H. A simple method for estimating fifty percent endpoints[J]. American Journal of Hygiene, 1938, 27: 493-497.
104. Rey, O., and D. P. Nayak. Nuclear retention of Ml protein in a temperature-sensitive mutant of influenza (A/WSN/33) virus does not affect nuclear export of viral ribonucleoproteins. J. Virol. 1992.66:5815-5824.
105. Rogers, G. N., J. C. Paulson, R. S. Daniels, J. J. Skehel, I. A. Wilson, and D. C. Wiley. Single amino acid substitutions in influenza haemagglutinin change receptor specificity. Nature 1983.304:76-78.
106. Rohm, C., J. Suss, V. Pohle, and R. G. Webster. 1996. Different hemagglutinin cleavage site variants of H7N7 in an influenza outbreak in Chickens in Leipzig, Germany. Virology 218:253-257.
107. Rottr. Molecular basis of infectivity and pathogenicity of myxoviruse. Veterinary Microbiology, 1992,(33):303-310.
108. Saito, T., and K. Kawano. Loss of glycosylation at Asnl44 alters the substrate preference of the N8 influenza A virus neuraminidase. J Vet Med Sci 1997.59: 923-926.
109. Sakaguchi, T., G. P. Leser, and R. A. Lamb. The ion channel activity of the influenza virus M2 protein affects transport through the Golgi apparatus. J. Cell Biol. 1996.133:733-747.
110. Scholtissek, C., W. Rohde, V. von Hoyningen, and R. Rott. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 1978.87: 13-20.
111. Seo, S. H., and R. G. Webster. Cross-reactive, cell-mediated immunity and protection of chickens from lethal H5N1 influenza virus infection in Hong Kong poultry markets. J Virol 2001.75: 2516-2525.
112. Seo, S. H., E. Hoffmann, and R. G. Webster. Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nature Medicine 2002a.8: 950-954.
113. Seo, S. H., M. Peiris, R. G. Webster. Protective cross-reactive cellular immunity to lethal A/Goose/Guangdong/1/96-like H5N1 influenza virus is correlated with the proportion of pulmonary CD8+ T cells expressing gamma interferon. J Virol 2002b.76: 4886-4890.
114. Shimbo, K., D. L. Brassard, R. A. Lamb, and L. H. Pinto. Ion selectivity and activation of the M2 ion channel of influenza virus. Biophys. J. 1996. 70:1335-1346.
115. Shinya K, Hamm S, Hatta M, Ito H, Ito T, Kawaoka Y., PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice. Virology. 2004. 320(2):258-66.
116. Skehel, J. J., D. J. Stevens, R. S. Daniels, A. R. Douglas, M. Knossow, I. A. Wilson, D. C. Wiley. A carbohydrate side chain on haemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. PNAS 1984.81: 1779-1783.
117. Slemons,R.D., Johnson,D.C., Osborne,J.S., Hayes,F. Type A influenza viruses isolated from wild freeflying ducks in California Avian Dis 1974.18:119-124.
118. Snyder, M. H, A. J. Buckler-White, W. T. London, E. L. Tierney, and B. R. Murphy. The avian influenza virus nucleoprotein gene and a specific constellation of avian and human virus polymerase genes each specify attenuation of avian-human influenza A/Pintail/79 reassortant viruses for monkeys. J Virol 1987.61: 2857-2863.
119. Steinhauer, D. A. Role of hemagglutinin cleavage for the pathogenicity of influenza virus. Virology 1999.258:1-20.
120. Stieneke-Grober, A., M. Vey, H. Angliker, E. Shaw, G. Thomas, C. Roberts, H. D. Klenk, and W. Garten. Influenza virus haemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease. EMBO J 1992; 11: 2407-2414.
121. Sturm-Ramirez K M., Ellis T., Bousfield B., et al. Reemerging H5Nlinfluenza viruses in Hong Kong in 2002 are highly pathogenic to ducks[J]. Journal of Virology, 2004, 78: 6988-6994.
122. Sturm-Ramirez, K.M., Ellis T., Bousfield, B., et al. Are Ducks Contributing to the Endemicity of Highly Pathogenic H5N1 Influenza Virus in Asia?. Journal of Virology, 2005, 79(17) :11269-11279.
123. Suarez, D. L., M. L. Perdue, N. Cox, T. Rowe, C. Bender, J. Huang, and D. E. Swayne. Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong. J. Virol. 1998.72:6678-6688.
124. Subbarao, E. K., W. London, and B. R. Murphy. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J. Virol. 1993. 67:1761-1764.
125. Subbarao, K., A. Klimov, J. Katz, H. Regnery, W. Lim, H. Hall, M. Perdue, D. Swayne, C. Bender, J. Huang, M. Hemphill, T. Rowe, M. Shaw, X. Xu, K. Fukuda, and N. Cox. Characterization of an Avian Influenza A (H5N1) Virus Isolated from a Child with a Fatal Respiratory Illness. Science 16 January 1998; 279: 393-396.
126. Swayne DE. Pathobiology of H5N2 Mexican avian influenza virus infections of chickens. Vet Pathol. 1997 Nov;34(6):557-67.
127. Takeda, M., A. Pekosz, K. ShuDK, L. H. Pinto, and R. A. Lamb. Influenza a virus M2 ion channel activity is essential for efficient replication in tissue culture. J Virol. 2002. 76:1391-9.
128. Talon,J., C. M. Horvath, R. Polley, C. F. Basler, T. Muster, P. Palese, and A. Garcia-Sastre. Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J Virol 2000.74:7989-7996.
129. Toth T E,Norcross N L.Precipitating and agglutinating activity in duck anti-soluble protein immune sera. Avian Dia,1981,25:338-352.
130. 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: 1-9.
131. Tu, Q., L. H. Pinto, G. Luo, M. A. Shaughnessy, D. Mullaney, S. Kurtz, M. Krystal, and R. A. Lamb. Characterization of inhibition of M2 ion channel activity by BL-1743, an inhibitor of influenza A virus. J. Virol. 1996.70:4246-4252.
132. Van Campen H,Easterday B C,Hinshaw V S.Destruction of lymphocytes by a virulent influenza A virus. Gen Viral, 1989a,70:467-472
133. Van Campen H,Easterday BC.Hinshaw VS.Virulent avian influenza A viruses:their effect on avian lymphocytes and macrophages in vivo and in vitro. J Gen Viral, 1989b,70:2 887-2 895.
134. Vines, A., K. Wells, M. Matrosovich, M. R Castrucci, T. Ito, and T. Kawaoka. The role of influenza A virus haemagglutinin residues 226 and 228 in receptor specificity and host range restriction. J Virol 1998.72: 7626-7631.
135. Wagner, R., T. Wolff, A. Herwig, S. Pleschka, and H. D. Klenk. Interdependence of haemagglutinin glycosylation and neuraminidase as regulators of influenza virus growth: a study by reverse genetics. J Virol 2000.74:6316-6323.
136. Wang X, Li M, Zheng H, Muster T, Palese P, Beg AA, Garcia-Sastre A. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J Virol. 2000. 74:11566-73.
137. Wang, C., K. Takeuchi, L. H. Pinto, and R. A. Lamb. Ion channel activity of influenza A virus M2 protein: characterization of the amantadine bloDK. J. Virol. 1993. 67:5585-5594.
138. Wang, C., R. A. Lamb, and L. H. Pinto. Activation of the M_2 ion channel of influenza virus: a role for the transmembrane domain histidine residue. Biophys. J. 1995.69:1363-1371.
139. Wang, C., R. A. Lamb, and L. H. Pinto. Direct measurement of the influenza A virus M_2 protein ion channel activity in mammalian cells. Virology 1994.205:133-140.
140. Watanabe, T. S., Watanabe, H. Ito, H. Kida, and Y. Kawaoka. Influenza A virus can undergo multiple cycles of replication without M2 ion channel activity. J Virol. 2001. 75:5656-62.
141. Webster, R.G., Evolution and ecology of influenza A viruses. Microbiol Reviews.1991. 56(1):152-154.
142. Webster, R. G., W. J. Bean, O. T. Gorman, T. M. Chambers,and Y. Kawaoka. Evolution and ecology of influenza A viruses. Microbiol.Rev. 1992. 56:152-179.
143. Webster, R.G., M.Yakhno,V.S. Hinshaw, et al. Intestinal influenza: replication and characterization of influenza viruses in ducks. Virology, 1978, 84:268-278.
144. Weis, W., Brown, J.H., Cusack, S., Paulson, J.C., Skehel, J.J. & Wiley, D.C. Structure of the influenza virus haemagglutinin complex with its receptor sialic acid. Nature, 1988.333: 426 -431.
145. Whittaker, G., I. Kemler, and A. Helenius. Hyperphosphorylation of mutant influenza virus matrix protein Ml causes its retention in the nucleus. J. Virol. 1995. 69:439-445.
146. Whittater, G., M. Bui, and A. Helenius. The role of nuclear import and export in influenza virus infection. Trends Cell Biol. 1996. 6:67-71.
147.Yao,Y.X.,L.J.Mingay,J.W.McCauley,and W.S.Barclay.Sequences in influenza A virus PB2protein that determine productive infection for an avian influenza virus in mouse and human cell lines J.Virol.2001.75:5410-5415.
148.Yasuda,J.,S.Nakada,A.Kato,T.Toyoda,and A.Ishthama.Molecular assembly of influenza virus:association of the NS2 protein with virion matrix.Virology.1993.196:249-255.
149.Zambon MC.Epidemiology and pathogenesis of influenza.J Antimicrob Chemother.1999.44SupplB:3-9.
150.Zhang,J.,and R.A.Lamb.Characterization of the membrane association of the influenza virus matrix protein in living cells.Virology.1996.225:255-266.
151.Zhirnov,O.P.Isolation of matrix protein M1 from influenza viruses by acid-dependent extraction with nonionic detergent.Virology.1992.186:324-330.
152.Zhou,N.N.,K.F.Shortridge,E.J.Claas,S.L.Krauss,and R.G.Webster.Rapid evolution of H5N1 influenza viruses in chickens in Hong Kong.J.Virol.1999.73:3366-3374.
153.陈义平,吴力力,万洪全,等.2002.实验性感染H9亚型禽流感病毒对鸡的免疫机能及免疫器官的影响[J].中国兽医学报.22(2):153-154.
154.甘孟侯.禽流感(第2版)[M].北京:中国农业出版社,2002.
155.李琦涵,姜莉.病毒感染的分子生物学[M].化学工业出版社,2004.
156.李泽君.H5N1亚型禽流感病毒跨越禽-哺乳动物种间屏障的遗传变异机制:[D].哈尔滨,中国农业科学院哈尔滨兽医研究所,2005.
157.刘超男,刘明,张云,等.H5N1亚型禽流感病毒的鸭致病性研究[J].中国农业科学,2006,39(2):412-417.
158.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[J].中国家禽,2007,29(15):1-7.
159.罗玲,胡薛英,程国富,等.H9N2亚型禽流感病毒人工感染蛋鸡的组织病理学研究[J].中国预防兽医学报.2004.26(4):259-262.
160.唐建霞,王幼明,黄克和.2004.实验性感染禽流感病毒抑制鸡的细胞免疫功能[J].江苏农业科学.1:75-78.
161.唐秀英,田国斌,赵传珊,等冲国禽流感流行株的分离鉴定[J].中国畜禽传染病,1998,20(1):1-5.
162.王永坤.鸭流感防治研究进展[J].辽宁畜牧兽医,2003,6:32-36.
2. Almond, J. W. A single gene determines the host range of influenza viruses. Nature. 1977. 270: 617-618.
3. Avalos R. T., Z. Yu, and D. P. Nayak. Association of influenza virus NP and Ml proteins with cellular cytoskeletal elements in influenza virus-infected cells. J Virol. 1997.71(4):2947-58
4. Baigent, S. J., R. C. Bethell, and J. W. McCauley. Genetic analysis reveals that both haemagglutinin and neuraminidase determine the sensitivity of naturally occurring avian influenza viruses to zanamivir in vitro. Virology 1999.263: 323-338.
5. Baigent, S.J., and J. W. McCauley. Glycosylation of haemagglutinin and stalk-length of neuraminidase combine to regulate the growth of avian influenza viruses in tissue culture. Virus Res 2001.79: 177-185.
6. Banks, J., Speidel E. C., McCauley J. W., and Alexander D. J.. Phylogenetic analysis of H7 haemagglutinin subtype influenza A viruses. Arch Virol 2000. 145: 1047-1058.
7. Baum,L. G., and J. C. Paulson. The N2 neuraminidase of human influenza viruses has acquired a substrate specificity complimentary to the haemagglutinin receptor specificity. Virology 1991.180: 10-15.
8. Bazzigher, L., A. Schwarz, and P. Staeheli. No enhanced influenza virus resistance of murine and avian cells expressing cloned duck Mx protein. Virology 1993.195: 100-112.
9. Beaton, A. R., and R. M. Krug. Transcription antitermination during influenza viral template RNA synthesis requires the nucleocapsid protein and the absence of a 5' capped end. Proc. Natl. Acad. Sci. USA 1986. 83:6282-6286.
10. Bennink, J. R., J. W. Yewdell, G. L. Smith, and B. Moss. Anti-influenza virus cytotoxic T lymphocytes recognize the three viral polymerases and a nonstructural protein: responsiveness to individual viral antigens is major histocompatibility complex controlled. J Virol 1987.61: 1098-1102.
11. Biswas S. K., P. L. Boutz, D.P. Nayak. Influenza virus nucleoprotein interacts with influenza virus polymerase proteins. J Virol. 1998.72:5493-5501.
12. Blok, J., and G. M. Air. Variation in the membrane-insertion and 'stalk' sequences in eight sub-types of influenza type A virus neuraminidase. Biochem 1982. 21: 4001-4007.
13. Brown CC, Olander HJ, Senne DA. A pathogenesis study of highly pathogenic avian influenza virus H5N2 in chickens, using immunohistochemistry. J Comp Pathol. 1992. 107(3):341-8.
14. Bui, M., G. Whittaker, and A. Helenius. Effect of Ml protein and low pH on nuclear transport of influenza virus ribonucleoproteins. J. Virol. 1996. 70:8391-8401.
15. Bukrinskaya, A. G., N. K. Vorkunova, G. V. Kornilayeva, R. A. Narmanbetova, and G. K..Bullido R, Gomez-Puertas P, Saiz MJ, Portela A. Influenza A virus NEP (NS2 protein) downregulates RNA synthesis of model template RNAs. J Virol. 2001. 75:4912-7.
16. Capua I, Mutinelli F. Mortality in Muscovy ducks (Cairina moschata) and domestic geese (Anser anser var. domesticus) associated with natural infection with a highly pathogenic avian influenza virus ofH7N1 subtype. Avian Pathology, 2001. 30: 179-183.
17. Castrucci, M. R., and Y. Kawaoka. Biologic importance of neuraminidase stalk length in influenza A virus. J Virol 1993. 67: 759-764.
18. Chen H., Deng G., Li Z., et al. The evolution of H5N1 influenza viruses in ducks in southern China. Proceedings of the National Academy of Sciences, U.S.A,2004.101(28), 10452-10457.
19. Chen, Z., Y. Li, and R. M. Krug. Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3'-end processing machinery. EMBO J. 1999.18:2273-2283
20. Cheung, C. Y., L. L. M. Poon, A. S. Lau, W. Luk, Y. L. Lau, K. F. Shortridge, S. Gordon, Y. Guan, J. S. M. Peiris. Induction of pro-inflammatory cytokines in human macrophages by influenza A (H5N1) viruses: a mechanism for the unusual severity of human disease? Lancet 2002.360: 1831-1837.
21. Chizhmakov, I. V., F. M. Geraghty, D. C. Ogden, A. Hayhurst, M. Antoniou, and A. J. Hay. Selective proton permeability and pH regulation of the influenza virus M2 channel expressed in mouse erythroleukaemia cells. J. Physiol. 1996.494:329-336.
22. Ciampor, F., C.A.Thompson, S. Grambas, and A. J.Hay. Regulation of pH by the M2 protein of influenza A viruses. Virus Res. 1992a. 22:247-258.
23. Ciampor, F., P. M. Bayley, M. V. Nermut, E. M. Hirst, R. J. Sugrue, and A. J. Hay. Evidence that the amantadine-induced, M2-mediated conversion of influenza A virus hemagglutinin to the low pH conformation occurs in an acidic trans Golgi compartment. Virology1992b. 188:14-24.
24. Claas, E., A. Osterhaus, R. van Beek, J. De Jong, , G. Rimmelzwaan, D. Senne, S. Krauss, K. Shortridge, and R. G Webster. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet 1998.351, 472-477.
25. Compans, R. W., and P. W. Choppin. 1975. Reproduction of myxoviruses, p. 179-252. In H. Fraenkel-Conrat, and R. R. Wagner (ed.), Comprehensive virology, vol. IV. Plenum Press, New York, N.Y.
26. Connor, R. J., Y. Kawaoka, R. G Webster, J. C. Paulson. Receptor specificity in human, avian and equine H2 and H3 influenza virus isolates. Virology 1994.205:17-23.
27. Criswell BS, Couch RB, Greenberg SB, Kimzey SL.The lymphocyte response to influenza in humans. Am Rev Respir Dis. 1979;120(3):700-4.
28. David L Suarez. Evolution of avian influenza viruses. Vet.Microbiol, 2003, 74:15- 27.
29. de la Luna, S., P. Fortes, A. Beloso, and J. Ortin. Influenza virus NS 1 protein enhances the rate of translation initiation of viral mRNAs. J. Virol. 1995.69:2427-2433.
30. Deborah MB, Eulogia R, Susan L. Swain CD4 T cell responses to influenza infection. Immunol . 2004. (16):171-177
31. Denis F, Alain S, Hantz S, et al. 2005. Antiviral vaccination and respiratory mucosal immunity: still disappointing results from a seductive idea.Press Med .34(17): 1245-1253
32. Dennis JA. How dangerous are avian influenza viruses for humans? [J].world poultry,2002,Special,l 1-12.
33. Desphande, K. L., V. A. Fried, M. Ando, and R. G. Webster. Glycosylation affects cleavage of an H5N2 influenza virus hemagglutinin and regulates virulence. Proc. Natl. Acad. Sci. USA 1987.84:36-40.
34. Eichelberger, M., W. Allan, M. Zijlstra, R. Jaenisch, and P. C. Doherty. Clearance of influenza virus respiratory infection in mice lacking class I major histocompatibility complex-restricted CD8~+ T cells. J Exp Med 1991. 174: 875-880.
35. Els, M. C., G. M. Air, K. G. Murti, R. G. Webster, and W. G. Laver. An 18-amino acid deletion in an influenza neuraminidase. Virology 1985. 142: 241-247.
36. Enami, K., T. A. Sato, S. Nakada, and M. Enami. Influenza virus NS1 protein stimulates translation of the M1 protein. J. Virol. 1994.68:1432-1437.
37. Fortes, P., A. Beloso, and J. Ortin. Influenza virus NS1 protein inhibits pre-mRNA splicing and bloDKs mRNA nucleocytoplasmic transport. EMBO J. 1994. 13:704-712.
38. Galarza J. M., A . Sowa, V. M. Hill, R. Skorko, and D.F. Summers. Influenza A virus NP protein expressed in insect cells by a recombinant baculovirus is associated with a protein kinase activity and possesses single-stranded RNA binding activity. Virus Res. 1992.24:91-106.
39. Garcia-Sastre, A., A. Egorov, D. Matassov, S. Brandt, D. E. Levy, J. E. Durbin, P. Palese, and T. Muster. Influenza A virus laDKing the NS1 gene replicates in interferon-deficient systems. Virology 1998.252:324-330.
40. Garten, W., and H.-D. Klenk. Understanding influenza virus pathogenicity. Trends Microbiol. 1999.7:99-100.
41. Goto, H., K. Wells, A. Takada, and Y. Kawaoka. Plasminogen-binding activity of neuraminidase determines the pathogenicity of influenza A virus. J Virol 2001. 75: 9297-9301.
42. Grambas, S., and A. J. Hay. Maturation of influenza A virus hemagglutinin-estimates of the pH encountered during transport and its regulation by the M2 protein. Virology. 1992a. 190:11 -18.
43. Grambas, S., M. S. Bennett, and A. J. Hay. Influence of amantadine resistance mutations on the pH regulatory function of the M2 protein of influenza A viruses. Virology. 1992b. 191:541-549.
44. Grey H M.Duck immunoglobulins I structural studies on a 5.7S and 7.8S g-globulin. J Immunol,1967,98:811-819.
45. Guo L, Lu X, Kang S M ,et al Enhancement of mucosal immune responses by chimeric influenza HA/SHIV virus-like particles. Virology,2003,313(2)1502-513.
46. Hatta, M., P. Gao, P. Halfmann, and Y. Kawaoka. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science 2001.293: 1840-1842.
47. Hay, A. J., B. Lomniczi, A. R. Bellamy, and J. J. Skehel. 1977. Transcription of the influenza virus genome. Virology 83:337-355.
48. Higgins D A,Shortridge K F,Ng PLK.Bile immunoglobulin of the duck (Anas platyrhynchos).II.Antibody response in influenza A virus infections. Immunology. 1987,62 :499-504.
49. Hinshaw VS, Webster RG, Naeve CW, Murphy BR. Altered tissue tropism of human-avian reassortant influenza viruses Virology. 1983 Jul 15;128(1):260-3.
50. Holsinger, L. J., D. Nichani, L. H. Pinto, and R. A. Lamb. Influenza A virus M2 ion channel protein: a structure-function analysis. J. Virol. 1994.68:1551-1563.
51. Holt, P S. Enhancement of chicken lymphocyte activation and lymphokine release by avian influenza virus. Dev Comp Immunol,1990.14:447-455.
52. Holt, P S, Larimer J M. Stimulatory effect Of avian influenza virus on chicken lymphocyte.Avian Dis,1989.33:743-749.
53. Homme, P J, Easterday B C. Avian influenza virus infections.IV.Response of pheasants,duck,and geese to influenza A-turkey-Wisconsin-1966 virus. Avian Dis. 1970.14,285-290.
54. Hooper PT, Russell GW, Selleck PW, Stanislawek WL.Observations on the relationship in chickens between the virulence of some avian influenza viruses and their pathogenicity for various organs.Avian Dis. 1995 Jul-Sep;39(3):458-64.
55. Horimoto, Y., Y. Yamazaki, T. Fukushima, T. Saito, S. E. Lindstrom, K. Omoe, R. Nerome, W. Lim, S. Sugita, and K. Nerome. Evolutionary characterization of the six internal genes of H5N1 human influenza A virus. J. Gen. Virol. 2000. 81:1293-1303.
56. Hughson, F.M.. Structural characterization of viral fusion proteins. Curr. Biol. 19955:265-274.
57. Hulse DJ., Webster RG, Russell RJ, Perez DR. Molecular determinants within the surface proteins involved in the pathogenicity of H5N1 influenza viruses in chickens. J Virol.2004. 78(18):9954-64.
58. Inkster, M. D., V. S. Hinshaw, and I. T. Schulze. The haemagglutinins of duck and human H1 influenza viruses differ in sequence conservation and in glycosylation. J Virol 1993.67: 7436-7443.
59. Kawaoka Y., C. W. Naeve, R. G. Webster. Is virulence of H5N2 influenza viruses in Chickens associated with loss of carbohydrate from the hemagglutinin? Virology. 1984. 139:303-16.
60. Kawaoka, Y., and R. G. Webster. Sequence requirements for cleavage activation of influenza virus hemagglutinin expressed in mammalian cells. Proc. Natl.Acad. Sci. USA 1988. 85:324-328.
61. Kawaoka, Y, O. T. Gorman, T. Ito, K. Wells, R. O. Donis, M. R. Castrucci, I. Donatelli, R. G. Webster. Influence of host species on the evolution of the nonstructural (NS) gene of influenza A viruses. Virus Res 1998: 55: 143-156.
62. Kawaoka, Y., S. Krauss, R. G. Webster. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol 1989.63: 4603-4608.
63. Kida H, Ito T, Yasuda J, et al, Potential for transmission of avian influenza viruses to pigs. J Gen Virol 1994, 75: 2183-2188.
64. Klenk, H.D., R. Rott, M. Orlich, and J. Blodorn. Activation of influenza A viruses by trypsin treatment. Virology 1975.68:426-439.
65. Ko, J.H., H.K. Jin, A. Asano, A. Takada, A. Ninomiya, H. Kida, H. Hokiyama, M. Ohara, M. Tsuzuki, M. Nishibori, M. Mitzutani, and T. Watanabe. Polymorphisms and the differential antiviral activity of the chicken Mx gene. Genome Res. 2002.12:595-601.
66. Kobasa, D., K. Wells, and Y. Kawaoka. Amino acids responsible for the absolute sialidase activity of the influenza A virus neuraminidase: relationship to growth in the duck intestine. J Virol 2001.75: 11773-11780.
67. Kobasa, D., S. Kodihalli, M. Luo, M. R. Castrucci, I. Donatelli, T. Suzuki, and Y. Kawaoka. Amino acid residues contributing to the substrate specificity of the influenza A neuraminidase. J Virol. 1999.73:6743-6751.
68. Krug, R. M. Priming of influenza viral RNA transcription by capped heterologous RNAs. Curr. Top. Microbiol. Immunol. 1981.93:125-149.
69. Krug, R. M., F. V. Alonso-Caplen, I. Julkunem, and M. G. Katze. Expression and replication of the influenza virus genome, p. 89-152. In R. M. Krug (ed.), The influenza viruses. Plenum Press, 1989.New York, N.Y.
70. Lamb, R. A., and R. M. Krug. Orthomyxoviridae: the viruses and their replication, p. 1353-1395. In B. N. Fields, D. M. Knipe, and P. M. Howley (ed.), 1996. Fields virology, 3rd ed. Lippincott-Raven, Philadelphia, Pa.
71. Laudert E, Sivaanandan V,Halvorson D.Effect of an H5N1 avian influenza virus infection on the immune system of mallard ducks. Avian Dis.1993. 37: 845-853.
72. Li Ze jun. Molecular basis of replication of Duck H5N1 influenza viruses in a mammalian model. Virol, 2005, 79(18): 12058-12064.
73. Li, S., M. Xu, and K. Coelingh. Electroporation of influenza virus ribonucleoprotein complexes for rescue of the nucleoprotein and matrix genes. Virus Res. 1995. 37:153-161.
74. Liang B, Hyland L, Hou S.Nasal-associated lymphoid tissue is a site of long-term virus-specific antibody production following respiratory virus infection of mice. J Virol. 2001 ;75(11):5416-20.
75. Lohmeyer, J., L. T. Talens, and H. D. Klenk. Biosynthesis of the influenza virus envelope in abortive infection. J. Gen. Virol. 1979.42:73-88.
76. Lu, Y., M. Wambach, M. G. Katze, and R. M. Krug. Binding of the influenza virus NS1 protein to double-stranded RNA inhibits the activation of the protein kinase that phosphorylated the eIF-2 translation initiation factor. Virology 1995.214: 222-228.
77. Lu, Y., X. Y. Qian, and R. M. Krug. The influenza virus NS1 protein: a novel inhibitor of pre-mRNA splicing. Genes Dev. 1994.8:1817-1828.
78. Ludwig, S., X. Wang, C. Ehrhardt, H. Zheng, N. Donelan, O. Planz, S. Pleschka, A. Garcia-Sastre, G. Heins, and T. Wolff. The influenza A virus NS 1 protein inhibits activation of Jun N-terminal kinase and AP-1 transcription factors. J Virol 2002.76: 11166-11171.
79. Martin, K., and A. Helenius. Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import. Cell 1991.67:117-130.
80. Massin P, van der Werf S, Naffakh N, Residue 627 of PB2 is a determinant of cold sensitivity in RNA replication of avian influenza viruses. J Virol. 2001;75(11):5398-404.
81. Matrosovich, M., N. Tuzikov, A. Bovin, A. Gambaryan, A. Klimov, M.R. Castrucci, I. Donatelli, and Y. Kawaoka. Early alterations of the receptor-binding properties of H1, H2, H3 avian influenza virus haemagglutinins after their introduction into mammals. J Virol 2000.74: 8502-8512.
82. Matsuo K, Iwasaki T, Asanuma H, Yoshikawa T, Chen Z, Tsujimoto H, Kurata T, Tamura SS. Cytokine mRNAs in the nasal-associated lymphoid tissue during influenza virus infection and nasal vaccination. Vaccine. 2000 Jan 31;18(14):1344-50.
83. Murphy, B. R., and R. G. Webster. Orthomyxoviruses, p. 1397-1445. In B. N. Fields, D. M. Knipe, and P. M. Howley (ed.), 1996.Fields virology, 3rd ed. Lippincott-Raven, Philadelphia, Pa.
84. Naffakh, N., P. Massin, N. Escriou, B. Crescenzo-Chaigne, and S. van der Werf. Genetic analysis of the compatibility between olymerase proteins from humans and avian strains of influenza A viruses. J. Gen. Virol. 2000. 81:1283-1291.
85. Neumann G, Hughes MT, Kawaoka Y. Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1. EMBO J. 2000. 19:6751-8.
86. Neumann, G, M. R. Castrucci, and Y. Kawaoka. Nuclear import and export of influenza virus nucleoprotein. J. Virol. 1997.71:9690-9700.
87. Nobusawa, E., T. Aoyama, H. Kato, Y. Suzuki, Y. Tateno, and K. Nakajima. Comparison of complete amino acid sequences and receptor-binding properties among 13 serotypes of haemagglutinins of influenza A viruses. Virology 1991.182:475-485.
88. Odagiri T, Tobita K. Mutation in NS2, a nonstructural protein of influenza A virus, extragenically causes aberrant replication and expression of the PA gene and leads to generation of defective interfering particles. Proc Natl Acad Sci U S A. 1990. 87:5988-92.
89. Ohuchi, M., A. Cramer, M. Vey, R. Ohuchi, W. Garten, and H.-D. Klenk. Rescue of vector-expressed fowl plague virus hemagglutinin in biologically active form by acidotropic agents and coexpressed M2 protein. J. Virol. 1994.68:920-926.
90. Ohuchi, M., R. Ohuchi, A. Feldmann, and H. K. Klenk. Regulation of receptor binding affinity of influenza virus haemagglutinin by its carbohydrate moiety. J Virol 1997.71:8377-8384.
91. Okazaki, K., Y. Kawaoka, R. G. Webster. Evolutionary pathways of the PA genes of influenza A viruses. Virology 1989.172: 601-608.
92. O'Neill, E., S. L. Krauss, J. M. Riberdy, R. G Webster, and D. L. Woodland. Heterologous protection against lethal A/HongKong/156/97 (H5N1) influenza virus infection in C57BL/6 mice. J Gen Virol 2000.81: 2689-2696.
93. O'Neill, R. E., J. Talon, and P. Palese. The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J. 1998. 17:288-296.
94. Park, Y. W., and M. G Katze. Translational control by influenza virus. Identification of cis-acting sequences and trans-acting factors which may regulate selective viral mRNA translation. J. Biol. Chem. 1995.270:28433-28439
95. Pensaert MK. Evidence for the natural transmission of influenza A virus from wild ducks to swine and itspotential importance for mam.Bull WHO ,1981,59:75-77.
96. Perdue, M. L., J. W. Latimer, and J. M. Crawford. A novel carbohydrate addition site of the haemagglutinin protein of a highly pathogenic H7 subtype avian influenza virus. Virology 1995. 213: 276-281.
97. Perkins L E, Swayne D E. Susceptibility of laughing gulls to H5N1 and H5N3 high pathogenic avian influenza viruses[J]. Avian Disease,2002, 46: 877-885.
98. Pilaipan P A, Prasert C C, Pakapak S,et al.Molecular Characterization of the Complete Genome of Human Influenza H5N1 Virus Isolates from Thailand [J].JGen Vi rol,2005,86:4232433.
99. Pinto, L. H., L. J. Holsinger, and R. A. Lamb. Influenza virus M2 protein has ion channel activity. Cell 1992.69:517-528.
100. Plotch, S. J., M. Bouley, and R. M. Krug. Transfer of 5'-terminal cap of globin mRNA to influenza viral complementary RNA during transcription in vitro. Proc Natl Acad Scr USA 1979.76:1618-1622.
101. Qiu, Y., and R. M. Krug. The influenza virus NS1 protein is a poly(A)-binding protein that inhibits nuclear export of mRNAs containing poly(A). J. Virol. 1994. 68:2425-2432
102. Qiu, Y, M. Nemeroff, and R. M. Krug. 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 1995.1:304-316.
103. Reed L J, Muench H. A simple method for estimating fifty percent endpoints[J]. American Journal of Hygiene, 1938, 27: 493-497.
104. Rey, O., and D. P. Nayak. Nuclear retention of Ml protein in a temperature-sensitive mutant of influenza (A/WSN/33) virus does not affect nuclear export of viral ribonucleoproteins. J. Virol. 1992.66:5815-5824.
105. Rogers, G. N., J. C. Paulson, R. S. Daniels, J. J. Skehel, I. A. Wilson, and D. C. Wiley. Single amino acid substitutions in influenza haemagglutinin change receptor specificity. Nature 1983.304:76-78.
106. Rohm, C., J. Suss, V. Pohle, and R. G. Webster. 1996. Different hemagglutinin cleavage site variants of H7N7 in an influenza outbreak in Chickens in Leipzig, Germany. Virology 218:253-257.
107. Rottr. Molecular basis of infectivity and pathogenicity of myxoviruse. Veterinary Microbiology, 1992,(33):303-310.
108. Saito, T., and K. Kawano. Loss of glycosylation at Asnl44 alters the substrate preference of the N8 influenza A virus neuraminidase. J Vet Med Sci 1997.59: 923-926.
109. Sakaguchi, T., G. P. Leser, and R. A. Lamb. The ion channel activity of the influenza virus M2 protein affects transport through the Golgi apparatus. J. Cell Biol. 1996.133:733-747.
110. Scholtissek, C., W. Rohde, V. von Hoyningen, and R. Rott. On the origin of the human influenza virus subtypes H2N2 and H3N2. Virology 1978.87: 13-20.
111. Seo, S. H., and R. G. Webster. Cross-reactive, cell-mediated immunity and protection of chickens from lethal H5N1 influenza virus infection in Hong Kong poultry markets. J Virol 2001.75: 2516-2525.
112. Seo, S. H., E. Hoffmann, and R. G. Webster. Lethal H5N1 influenza viruses escape host anti-viral cytokine responses. Nature Medicine 2002a.8: 950-954.
113. Seo, S. H., M. Peiris, R. G. Webster. Protective cross-reactive cellular immunity to lethal A/Goose/Guangdong/1/96-like H5N1 influenza virus is correlated with the proportion of pulmonary CD8+ T cells expressing gamma interferon. J Virol 2002b.76: 4886-4890.
114. Shimbo, K., D. L. Brassard, R. A. Lamb, and L. H. Pinto. Ion selectivity and activation of the M2 ion channel of influenza virus. Biophys. J. 1996. 70:1335-1346.
115. Shinya K, Hamm S, Hatta M, Ito H, Ito T, Kawaoka Y., PB2 amino acid at position 627 affects replicative efficiency, but not cell tropism, of Hong Kong H5N1 influenza A viruses in mice. Virology. 2004. 320(2):258-66.
116. Skehel, J. J., D. J. Stevens, R. S. Daniels, A. R. Douglas, M. Knossow, I. A. Wilson, D. C. Wiley. A carbohydrate side chain on haemagglutinins of Hong Kong influenza viruses inhibits recognition by a monoclonal antibody. PNAS 1984.81: 1779-1783.
117. Slemons,R.D., Johnson,D.C., Osborne,J.S., Hayes,F. Type A influenza viruses isolated from wild freeflying ducks in California Avian Dis 1974.18:119-124.
118. Snyder, M. H, A. J. Buckler-White, W. T. London, E. L. Tierney, and B. R. Murphy. The avian influenza virus nucleoprotein gene and a specific constellation of avian and human virus polymerase genes each specify attenuation of avian-human influenza A/Pintail/79 reassortant viruses for monkeys. J Virol 1987.61: 2857-2863.
119. Steinhauer, D. A. Role of hemagglutinin cleavage for the pathogenicity of influenza virus. Virology 1999.258:1-20.
120. Stieneke-Grober, A., M. Vey, H. Angliker, E. Shaw, G. Thomas, C. Roberts, H. D. Klenk, and W. Garten. Influenza virus haemagglutinin with multibasic cleavage site is activated by furin, a subtilisin-like endoprotease. EMBO J 1992; 11: 2407-2414.
121. Sturm-Ramirez K M., Ellis T., Bousfield B., et al. Reemerging H5Nlinfluenza viruses in Hong Kong in 2002 are highly pathogenic to ducks[J]. Journal of Virology, 2004, 78: 6988-6994.
122. Sturm-Ramirez, K.M., Ellis T., Bousfield, B., et al. Are Ducks Contributing to the Endemicity of Highly Pathogenic H5N1 Influenza Virus in Asia?. Journal of Virology, 2005, 79(17) :11269-11279.
123. Suarez, D. L., M. L. Perdue, N. Cox, T. Rowe, C. Bender, J. Huang, and D. E. Swayne. Comparisons of highly virulent H5N1 influenza A viruses isolated from humans and chickens from Hong Kong. J. Virol. 1998.72:6678-6688.
124. Subbarao, E. K., W. London, and B. R. Murphy. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J. Virol. 1993. 67:1761-1764.
125. Subbarao, K., A. Klimov, J. Katz, H. Regnery, W. Lim, H. Hall, M. Perdue, D. Swayne, C. Bender, J. Huang, M. Hemphill, T. Rowe, M. Shaw, X. Xu, K. Fukuda, and N. Cox. Characterization of an Avian Influenza A (H5N1) Virus Isolated from a Child with a Fatal Respiratory Illness. Science 16 January 1998; 279: 393-396.
126. Swayne DE. Pathobiology of H5N2 Mexican avian influenza virus infections of chickens. Vet Pathol. 1997 Nov;34(6):557-67.
127. Takeda, M., A. Pekosz, K. ShuDK, L. H. Pinto, and R. A. Lamb. Influenza a virus M2 ion channel activity is essential for efficient replication in tissue culture. J Virol. 2002. 76:1391-9.
128. Talon,J., C. M. Horvath, R. Polley, C. F. Basler, T. Muster, P. Palese, and A. Garcia-Sastre. Activation of interferon regulatory factor 3 is inhibited by the influenza A virus NS1 protein. J Virol 2000.74:7989-7996.
129. Toth T E,Norcross N L.Precipitating and agglutinating activity in duck anti-soluble protein immune sera. Avian Dia,1981,25:338-352.
130. 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: 1-9.
131. Tu, Q., L. H. Pinto, G. Luo, M. A. Shaughnessy, D. Mullaney, S. Kurtz, M. Krystal, and R. A. Lamb. Characterization of inhibition of M2 ion channel activity by BL-1743, an inhibitor of influenza A virus. J. Virol. 1996.70:4246-4252.
132. Van Campen H,Easterday B C,Hinshaw V S.Destruction of lymphocytes by a virulent influenza A virus. Gen Viral, 1989a,70:467-472
133. Van Campen H,Easterday BC.Hinshaw VS.Virulent avian influenza A viruses:their effect on avian lymphocytes and macrophages in vivo and in vitro. J Gen Viral, 1989b,70:2 887-2 895.
134. Vines, A., K. Wells, M. Matrosovich, M. R Castrucci, T. Ito, and T. Kawaoka. The role of influenza A virus haemagglutinin residues 226 and 228 in receptor specificity and host range restriction. J Virol 1998.72: 7626-7631.
135. Wagner, R., T. Wolff, A. Herwig, S. Pleschka, and H. D. Klenk. Interdependence of haemagglutinin glycosylation and neuraminidase as regulators of influenza virus growth: a study by reverse genetics. J Virol 2000.74:6316-6323.
136. Wang X, Li M, Zheng H, Muster T, Palese P, Beg AA, Garcia-Sastre A. Influenza A virus NS1 protein prevents activation of NF-kappaB and induction of alpha/beta interferon. J Virol. 2000. 74:11566-73.
137. Wang, C., K. Takeuchi, L. H. Pinto, and R. A. Lamb. Ion channel activity of influenza A virus M2 protein: characterization of the amantadine bloDK. J. Virol. 1993. 67:5585-5594.
138. Wang, C., R. A. Lamb, and L. H. Pinto. Activation of the M_2 ion channel of influenza virus: a role for the transmembrane domain histidine residue. Biophys. J. 1995.69:1363-1371.
139. Wang, C., R. A. Lamb, and L. H. Pinto. Direct measurement of the influenza A virus M_2 protein ion channel activity in mammalian cells. Virology 1994.205:133-140.
140. Watanabe, T. S., Watanabe, H. Ito, H. Kida, and Y. Kawaoka. Influenza A virus can undergo multiple cycles of replication without M2 ion channel activity. J Virol. 2001. 75:5656-62.
141. Webster, R.G., Evolution and ecology of influenza A viruses. Microbiol Reviews.1991. 56(1):152-154.
142. Webster, R. G., W. J. Bean, O. T. Gorman, T. M. Chambers,and Y. Kawaoka. Evolution and ecology of influenza A viruses. Microbiol.Rev. 1992. 56:152-179.
143. Webster, R.G., M.Yakhno,V.S. Hinshaw, et al. Intestinal influenza: replication and characterization of influenza viruses in ducks. Virology, 1978, 84:268-278.
144. Weis, W., Brown, J.H., Cusack, S., Paulson, J.C., Skehel, J.J. & Wiley, D.C. Structure of the influenza virus haemagglutinin complex with its receptor sialic acid. Nature, 1988.333: 426 -431.
145. Whittaker, G., I. Kemler, and A. Helenius. Hyperphosphorylation of mutant influenza virus matrix protein Ml causes its retention in the nucleus. J. Virol. 1995. 69:439-445.
146. Whittater, G., M. Bui, and A. Helenius. The role of nuclear import and export in influenza virus infection. Trends Cell Biol. 1996. 6:67-71.
147.Yao,Y.X.,L.J.Mingay,J.W.McCauley,and W.S.Barclay.Sequences in influenza A virus PB2protein that determine productive infection for an avian influenza virus in mouse and human cell lines J.Virol.2001.75:5410-5415.
148.Yasuda,J.,S.Nakada,A.Kato,T.Toyoda,and A.Ishthama.Molecular assembly of influenza virus:association of the NS2 protein with virion matrix.Virology.1993.196:249-255.
149.Zambon MC.Epidemiology and pathogenesis of influenza.J Antimicrob Chemother.1999.44SupplB:3-9.
150.Zhang,J.,and R.A.Lamb.Characterization of the membrane association of the influenza virus matrix protein in living cells.Virology.1996.225:255-266.
151.Zhirnov,O.P.Isolation of matrix protein M1 from influenza viruses by acid-dependent extraction with nonionic detergent.Virology.1992.186:324-330.
152.Zhou,N.N.,K.F.Shortridge,E.J.Claas,S.L.Krauss,and R.G.Webster.Rapid evolution of H5N1 influenza viruses in chickens in Hong Kong.J.Virol.1999.73:3366-3374.
153.陈义平,吴力力,万洪全,等.2002.实验性感染H9亚型禽流感病毒对鸡的免疫机能及免疫器官的影响[J].中国兽医学报.22(2):153-154.
154.甘孟侯.禽流感(第2版)[M].北京:中国农业出版社,2002.
155.李琦涵,姜莉.病毒感染的分子生物学[M].化学工业出版社,2004.
156.李泽君.H5N1亚型禽流感病毒跨越禽-哺乳动物种间屏障的遗传变异机制:[D].哈尔滨,中国农业科学院哈尔滨兽医研究所,2005.
157.刘超男,刘明,张云,等.H5N1亚型禽流感病毒的鸭致病性研究[J].中国农业科学,2006,39(2):412-417.
158.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[J].中国家禽,2007,29(15):1-7.
159.罗玲,胡薛英,程国富,等.H9N2亚型禽流感病毒人工感染蛋鸡的组织病理学研究[J].中国预防兽医学报.2004.26(4):259-262.
160.唐建霞,王幼明,黄克和.2004.实验性感染禽流感病毒抑制鸡的细胞免疫功能[J].江苏农业科学.1:75-78.
161.唐秀英,田国斌,赵传珊,等冲国禽流感流行株的分离鉴定[J].中国畜禽传染病,1998,20(1):1-5.
162.王永坤.鸭流感防治研究进展[J].辽宁畜牧兽医,2003,6:32-36.