The PB2, PA, HA, NP, and NS genes of a highly pathogenic avian influenza virus A/whooper swan/Mongolia/3/2005 (H5N1) are responsible for pathogenicity in ducks

Virology Journal

Hiroshi Kida⁴  Ayato Takada⁴  Masatoshi Okamatsu²  Kenji Minari²  Kosuke Soda¹  Yoshihiro Sakoda²  Masahiro Kajihara³ 

[1] Present address: Avian Zoonosis Research Center, Faculty of Agriculture, Tottori University, Tottori, 680-8553, Japan;Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Hokkaido, 060-0818, Japan;Present address: Division of Global Epidemiology, Research Center for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, 001-0020, Japan;Research Center for Zoonosis Control, Hokkaido University, Sapporo, Hokkaido, 001-0020, Japan

关键词: Pathogenicity;    Natural host;    Duck;    H5N1 influenza virus;   

Others  :  1151985
DOI  :  10.1186/1743-422X-10-45

 received in 2012-07-11, accepted in 2013-01-28,  发布年份 2013

【 摘 要 】

Background

Wild ducks are the natural hosts of influenza A viruses. Duck influenza, therefore, has been believed inapparent infection with influenza A viruses, including highly pathogenic avian influenza viruses (HPAIVs) in chickens. In fact, ducks experimentally infected with an HPAIV strain, A/Hong Kong/483/1997 (H5N1) (HK483), did not show any clinical signs. Another HPAIV strain, A/whooper swan/Mongolia/3/2005 (H5N1) (MON3) isolated from a dead swan, however, caused neurological dysfunction and death in ducks.

Method

To understand the mechanism whereby MON3 shows high pathogenicity in ducks, HK483, MON3, and twenty-four reassortants generated between these two H5N1 viruses were compared for their pathogenicity in domestic ducks.

Results

None of the ducks infected with MON3-based single-gene reassortants bearing the PB2, NP, or NS gene segment of HK483 died, and HK483-based single-gene reassortants bearing PB2, NP, or NS genes of MON3 were not pathogenic in ducks, suggesting that multiple gene segments contribute to the pathogenicity of MON3 in ducks. All the ducks infected with the reassortant bearing PB2, PA, HA, NP, and NS gene segments of MON3 died within five days post-inoculation, as did those infected with MON3. Each of the viruses was assessed for replication in ducks three days post-inoculation. MON3 and multi-gene reassortants pathogenic in ducks were recovered from all of the tissues examined and replicated with high titers in the brains and lungs.

Conclusion

The present results indicate that multigenic factors are responsible for efficient replication of MON3 in ducks. In particular, virus growth in the brain might correlate with neurological dysfunction and the disease severity.

【 授权许可】

   
2013 Kajihara et al.; licensee BioMed Central Ltd.

【 图 表 】

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【 参考文献 】

• [1]Kawaoka Y, Cox NJ, Haller O, Hongo S, Kaverin N, Klenk HD, Lamb RA, McCauley J, Palese P, Rimstad E, Webster RG: Family Orthomyxoviridae. In Virus Taxonomy. 8th edition. Edited by Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Ball LA. California: Elsevier Academic Press; 2005:681-693.
• [2]Fouchier RA, Munster V, Wallensten A, Bestebroer TM, Herfst S, Smith D, Rimmelzwaan GF, Olsen B, Osterhaus AD: Characterization of a novel influenza A virus hemagglutinin subtype (H16) obtained from black-headed gulls. J Virol 2005, 79:2814-2822.
• [3]Ito T, Okazaki K, Kawaoka Y, Takada A, Webster RG, Kida H: Perpetuation of influenza A viruses in Alaskan waterfowl reservoirs. Arch Virol 1995, 140:1163-1172.
• [4]Okazaki K, Takada A, Ito T, Imai M, Takakuwa H, Hatta M, Ozaki H, Tanizaki T, Nagano T, Ninomiya A, Demenov VA, Tyaptirganov MM, Karatayeva TD, Yamnikova SS, Lvov DK, Kida H: Precursor genes of future pandemic influenza viruses are perpetuated in ducks nesting in Siberia. Arch Virol 2000, 145:885-893.
• [5]Kida H, Yanagawa R, Matsuoka Y: Duck influenza lacking evidence of disease signs and immune response. Infect Immun 1980, 30:547-553.
• [6]Kida H, Kawaoka Y, Neave CW, Webster RG: Antigenic and genetic conservation of H3 influenza virus in wild ducks. Virology 1987, 159:109-119.
• [7]Kida H: Ecology of influenza viruses in nature, birds, and humans. Glob Environ Res 2008, 12:9-14.
• [8]Alexander DJ: A review of avian influenza in different bird species. Vet Microbiol 2000, 74:3-13.
• [9]Shortridge KF, Zhou NN, 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 RG: Characterization of avian H5N1 influenza viruses from poultry in Hong Kong. Virology 1998, 252:331-342.
• [10]Centers for Disease Conrrol and Prevention (CDC): Isolation of avian influenza A(H5N1) viruses from humans--Hong Kong, May-December 1997. MMWR Morb Mortal Wkly Rep 1997, 46:1204-1207.
• [11]Webster RG, Govorkova EA: H5N1 influenza–continuing evolution and spread. N Engl J Med 2006, 355:2174-2177.
• [12]Kishida N, Sakoda Y, Isoda N, Matsuda K, Eto M, Sunaga Y, Umemura T, Kida H: Pathogenicity of H5 influenza viruses for ducks. Arch Virol 2005, 150:1383-1392.
• [13]Sturm-Ramirez KM, Ellis T, Bousfield B, Bissett L, Dyrting K, Rehg JE, Poon L, Guan Y, Peiris M, Webster RG: Reemerging H5N1 influenza viruses in Hong Kong in 2002 are highly pathogenic to ducks. J Virol 2004, 78:4892-4901.
• [14]Chen H, Smith GJ, Zhang SY, Qin K, Wang J, Li KS, Webster RG, Peiris JS, Guan Y: Avian flu: H5N1 virus outbreak in migratory waterfowl. Nature 2005, 436:191-192.
• [15]Liu J, Xiao H, Lei F, Zhu Q, Qin K, Zhang XW, Zhang XL, Zhao D, Wang G, Feng Y, Ma J, Liu W, Wang J, Gao GF: Highly pathogenic H5N1 influenza virus infection in migratory birds. Science 2005, 309:1206.
• [16]Wang G, Zhan D, Li L, Lei F, Liu B, Liu D, Xiao H, Feng Y, Li J, Yang B, Yin Z, Song X, Zhu X, Cong Y, Pu J, Wang J, Liu J, Gao GF, Zhu Q: H5N1 avian influenza re-emergence of Lake Qinghai: phylogenetic and antigenic analyses of the newly isolated viruses and roles of migratory birds in virus circulation. J Gen Virol 2008, 89:697-702.
• [17]Sakoda Y, Sugar S, Batchluun D, Erdene-Ochir TO, Okamatsu M, Isoda N, Soda K, Takakuwa H, Tsuda Y, Yamamoto N, Kishida N, Matsuno K, Nakayama E, Kajihara M, Yokoyama A, Takada A, Sodnomdarjaa R, Kida H: Characterization of H5N1 highly pathogenic avian influenza virus strains isolated from migratory waterfowl in Mongolia on the way back from the southern Asia to their northern territory. Virology 2010, 406:88-94.
• [18]Okamatsu M, Tanaka T, Yamamoto N, Sakoda Y, Sasaki T, Tsuda Y, Isoda N, Kokumai N, Takada A, Umemura T, Kida H: Antigenic, genetic, and pathogenic characterization of H5N1 highly pathogenic avian influenza viruses isolated from dead whooper swans (Cygnus cygnus) found in northern Japan in 2008. Virus Genes 2010, 41:351-357.
• [19]Uchida Y, Mase M, Yoneda K, Kimura A, Obara T, Kumagai S, Saito T, Yamamoto Y, Nakamura K, Tsukamoto K, Yamaguchi S: Highly pathogenic avian influenza virus (H5N1) isolated from whooper swans. Japan. Emerg Infect Dis 2008, 14:1427-1429.
• [20]Senne DA, Panigrahy B, Kawaoka Y, Pearson JE, Suss J, Lipkind M, Kida H, Webster RG: Survey of the hemagglutinin (HA) cleavage site sequence of H5 and H7 avian influenza viruses: amino acid sequence at the HA cleavage site as a marker of pathogenicity potential. Avian Dis 1996, 40:425-437.
• [21]Park CH, Ozaki H, Takada A, Kida H, Ochiai K, Umemura T: Primary target cells of virulent strains of type A influenza virus in chicken embryos. Avian Pathol 2001, 30:269-272.
• [22]Muramoto Y, Ozaki H, Takada A, Park CH, Sunden Y, Umemura T, Kawaoka Y, Matsuda H, Kida H: Highly pathogenic H5N1 influenza virus causes coagulopathy in chickens. Microbiol Immunol 2006, 50:73-81.
• [23]Hulse-Post DJ, Franks J, Boyd K, Salomon R, Hoffmann E, Yen HL, Webby RJ, Walker D, Nguyen TD, Webster RG: Molecular changes in the polymerase genes (PA and PB1) associated with high pathogenicity of H5N1 influenza virus in mallard ducks. J Virol 2007, 81:8515-8524.
• [24]Marjuki H, Scholtissek C, Franks J, Negovetich NJ, Aldridge JR, Salomon R, Finkelstein D, Webster RG: Three amino acid changes in PB1-F2 of highly pathogenic H5N1 avian influenza virus affect pathogenicity in mallard ducks. Arch Virol 2010, 155:925-934.
• [25]Song J, Feng H, Xu J, Zhao D, Shi J, Li Y, Deng G, Jiang Y, Li X, Zhu P, Guan Y, Bu Z, Kawaoka Y, Chen H: The PA protein directly contributes to the virulence of H5N1 avian influenza viruses in domestic ducks. J Virol 2011, 85:2180-2188.
• [26]Snyder MH, Buckler-White AJ, London WT, Tierney EL, Murphy BR: 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.
• [27]Salomon R, Franks J, Govorkova EA, Ilyushina NA, Yen HL, Hulse-Post DJ, Humberd J, Trichet M, Rehg JE, Webby RJ, Webster RG, Hoffmann E: The polymerase complex genes contribute to the high virulence of the human H5N1 influenza virus isolate A/Vietnam/1203/04. J Exp Med 2006, 203:689-697.
• [28]Rudneva IA, Timofeeva TA, Shilov AA, Kochergin-Nikitsky KS, Varich NL, Ilyushina NA, Gambaryan AS, Krylov PS, Kaverin NV: Effect of gene constellation and postreassortment amino acid change on the phenotypic features of H5 influenza virus reassortants. Arch Virol 2007, 152:1139-1145.
• [29]Maines TR, Chen LM, Belser JA, Van Hoeven N, Smith E, Donis RO, Tumpey TM, Katz JM: Multiple genes contribute to the virulent phenotype observed in ferrets of an H5N1 influenza virus isolated from Thailand in 2004. Virology 2011, 413:226-230.
• [30]Wasilenko JL, Lee CW, Sarmento L, Spackman E, Kapczynski DR, Suarez DL, Pantin-Jackwood MJ: NP, PB1, and PB2 viral genes contribute to altered replication of H5N1 avian influenza viruses in chickens. J Virol 2008, 82:4544-4553.
• [31]Tada T, Suzuki K, Sakurai Y, Kubo M, Okada H, Itoh T, Tsukamoto K: NP body domain and PB2 contribute to increased virulence of H5N1 highly pathogenic avian influenza viruses in chickens. J Virol 2011, 85:1834-1846.
• [32]Gabriel G, Klingel K, Otte A, Thiele S, Hudjetz B, Arman-Kalcek G, Sauter M, Shmidt T, Rother F, Baumgarte S, Keiner B, Hartmann E, Bader M, Brownlee GG, Fodor E, Klenk HD: Differential use of importin-α isoforms governs cell tropism and host adaptation of influenza virus. Nat Commun 2011, 2:156.
• [33]Sarmento L, Wasilenko J, Pantin-Jackwood M: The effects of NS gene exchange on the pathogenicity of H5N1 HPAI viruses in ducks. Avian Dis 2010, 54(Suppl 1):532-537.
• [34]Hale BG, Randall RE, Ortín J, Jackson D: The multifunctional NS1 protein of influenza A viruses. J Gen Virol 2008, 89:2359-2376.
• [35]Long JX, Peng DX, Liu YL, Wu YT, Liu XF: Virulence of H5N1 avian influenza virus enhanced by a 15-nucleotide deletion in the viral nonstructural gene. Virus Genes 2008, 36:471-478.
• [36]Barber MR, Aldridge JR Jr, Webster RG, Magor KE: Association of RIG-I with innate immunity of ducks to influenza. Proc Natl Acad Sci USA 2010, 107:5913-5918.
• [37]Pantin-Jackwood MJ, Suarez DL, Spackman E, Swayne DE: Age at infection affects the pathogenicity of Asian highly pathogenic avian influenza H5N1 viruses in ducks. Virus Res 2007, 130:151-161.
• [38]Yuen KY, Chan PK, Peiris M, Tsang DN, Que TL, Shortridge KF, Cheung PT, To WK, Ho ET, Sung R, Cheng AF: Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet 1998, 351:467-471.
• [39]To KF, Chan PK, Chan KF, Lee WK, Lam WY, Wong KF, Tang NL, Tsang DN, Sung RY, Buckley TA, Tam JS, Cheng AF: Pathology of fatal human infection associated with avian influenza A H5N1 virus. J Med Virol 2001, 63:242-246.
• [40]Kajihara M, Matsuno K, Simulundu E, Muramatsu M, Noyori O, Manzoor R, Nakayama E, Igarashi M, Tomabechi D, Yoshida R, Okamatsu M, Sakoda Y, Ito K, Kida H, Takada A: An H5N1 highly pathogenic avian influenza virus that invaded Japan through waterfowl migration. Jpn J Vet Res 2011, 59:89-100.
• [41]Tsuda Y, Isoda N, Sakoda Y, Kida H: Factors responsible for plaque formation of A/duck/Siberia/272/1998 (H13N6) influenza virus on MDCK cells. Virus Res 2009, 140:194-198.
• [42]Hoffmann E, Neumann G, Kawaoka Y, Hobom G, Webster RG: A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci USA 2000, 97:6108-6113.
• [43]Reed LJ, Muench H: A simple method of estimating 50 per cent end-points. Am J Hyg 1938, 27:493-497.