Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2009 May 27;52(5):428–438. doi: 10.1007/s11427-009-0062-z

Interspecies transmission and host restriction of avian H5N1 influenza virus

Di Liu 1, XiaoLing Liu 1, JingHua Yan 1, Wen-Jun Liu 1,, George Fu Gao 1,2,
PMCID: PMC7089370  PMID: 19471865

Abstract

Long-term endemicity of avian H5N1 influenza virus in poultry and continuous sporadic human infections in several countries has raised the concern of another potential pandemic influenza. Suspicion of the avian origin of the previous pandemics results in the close investigation of the mechanism of interspecies transmission. Entry and fusion is the first step for the H5N1 influenza virus to get into the host cells affecting the host ranges. Therefore receptor usage study has been a major focus for the last few years. We now know the difference of the sialic acid structures and distributions in different species, even in the different parts of the same host. Many host factors interacting with the influenza virus component proteins have been identified and their role in the host range expansion and interspecies transmission is under detailed scrutiny. Here we review current progress in the receptor usage and host factors.

Keywords: H5N1 influenza virus, interspecies transmission, virus adaptation, host factors

Footnotes

Supported by the National Basic Research Program of China (Grant Nos. 2005CB523001, 2005CB523002), National Key Technologies Research & Development Program (Grant 2006BAD06A01/2006BAD06A04); US National Institutes of Health (NIH) (Grant 3 U19 AI051915-05S1), the National Natural Science Foundation of China (Grant 30599434). GAO FG is a distinguished young investigator of the NSFC (Grant No. 30525010).

Contributor Information

Wen-Jun Liu, Email: liuwj@im.ac.cn.

George Fu Gao, Email: gaof@im.ac.cn.

References

  • 1.Kawaoka Y., Krauss S., Webster R. G. Avian-to-human transmission of the PB1 gene of influenza A viruses in the 1957 and 1968 pandemics. J Virol. 1989;63(11):4603–4608. doi: 10.1128/jvi.63.11.4603-4608.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 2.Chang S., Zhang J., Liao X., et al. Influenza Virus Database (IVDB): an integrated information resource and analysis platform for influenza virus research. Nucleic Acids Res. 2007;35(Databaseissue):D376–380. doi: 10.1093/nar/gkl779. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 3.Bao Y., Bolotov P., Dernovoy D., et al. The influenza virus resource at the National Center for Biotechnology Information. J Virol. 2008;82(2):596–601. doi: 10.1128/JVI.02005-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 4.Obenauer J. C., Denson J., Mehta P. K., et al. Large-scale sequence analysis of avian influenza isolates. Science. 2006;311(5767):1576–1580. doi: 10.1126/science.1121586. [DOI] [PubMed] [Google Scholar]
  • 5.Xu X., Subbarao, Cox N. J., et al. Genetic characterization of the pathogenic influenza A/Goose/Guangdong/1/96 (H5N1) virus: similarity of its hemagglutinin gene to those of H5N1 viruses from the 1997 outbreaks in Hong Kong. Virology. 1999;261(1):15–19. doi: 10.1006/viro.1999.9820. [DOI] [PubMed] [Google Scholar]
  • 6.Yee K. S., Carpenter T. E., Cardona C. J. Epidemiology of H5N1 avian influenza. Comp Immunol Microbiol Infect Dis. 2009;32(4):325–340. doi: 10.1016/j.cimid.2008.01.005. [DOI] [PubMed] [Google Scholar]
  • 7.Zhu Q. Y., Qin E. D., Wang W., et al. Fatal infection with influenza A (H5N1) virus in China. N Engl J Med. 2006;354(25):2731–2732. doi: 10.1056/NEJMc066058. [DOI] [PubMed] [Google Scholar]
  • 8.Chen H., Deng G., Li Z., et al. The evolution of H5N1 influenza viruses in ducks in southern China. Proc Natl Acad Sci USA. 2004;101(28):10452–10457. doi: 10.1073/pnas.0403212101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 9.Chen H., Li Y., Li Z., et al. Properties and dissemination of H5N1 viruses isolated during an influenza outbreak in migratory waterfowl in western China. J Virol. 2006;80(12):5976–5983. doi: 10.1128/JVI.00110-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 10.Chen H., Smith G. J., Zhang S. Y., et al. Avian flu: H5N1 virus outbreak in migratory waterfowl. Nature. 2005;436(7048):191–192. doi: 10.1038/nature03974. [DOI] [PubMed] [Google Scholar]
  • 11.Liu J., Xiao H., Lei F., et al. Highly pathogenic H5N1 influenza virus infection in migratory birds. Science. 2005;309(5738):1206. doi: 10.1126/science.1115273. [DOI] [PubMed] [Google Scholar]
  • 12.Wang G., Zhan D., Li L., et al. 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(Pt3):697–702. doi: 10.1099/vir.0.83419-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13.Subbarao K., Klimov A., Katz J., et al. Characterization of an avian influenza A (H5N1) virus isolated from a child with a fatal respiratory illness. Science. 1998;279(5349):393–396. doi: 10.1126/science.279.5349.393. [DOI] [PubMed] [Google Scholar]
  • 14.Yuen K. Y., Chan P. K., Peiris M., et al. Clinical features and rapid viral diagnosis of human disease associated with avian influenza A H5N1 virus. Lancet. 1998;351(9101):467–471. doi: 10.1016/s0140-6736(98)01182-9. [DOI] [PubMed] [Google Scholar]
  • 15.Claas E. C., Osterhaus A. D., van Beek R., et al. Human influenza A H5N1 virus related to a highly pathogenic avian influenza virus. Lancet. 1998;351(9101):472–477. doi: 10.1016/S0140-6736(97)11212-0. [DOI] [PubMed] [Google Scholar]
  • 16.de Jong J. C., Claas E. C., Osterhaus A. D., et al. A pandemic warning? Nature. 1997;389(6651):554. doi: 10.1038/39218. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 17.de Jong M. D., Simmons C. P., Thanh T. T., et al. Fatal outcome of human influenza A (H5N1) is associated with high viral load and hypercyto-kinemia. Nat Med. 2006;12(10):1203–1207. doi: 10.1038/nm1477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 18.Buxton Bridges C., Katz J. M., Seto W. H., et al. Risk of influenza A (H5N1) infection among health care workers exposed to patients with influenza A (H5N1), Hong Kong. J Infect Dis. 2000;181(1):344–348. doi: 10.1086/315213. [DOI] [PubMed] [Google Scholar]
  • 19.Ungchusak K., Auewarakul P., Dowell S. F., et al. Probable person-to-person transmission of avian influenza A (H5N1) N Engl J Med. 2005;352(4):333–340. doi: 10.1056/NEJMoa044021. [DOI] [PubMed] [Google Scholar]
  • 20.Kandun I. N., Wibisono H., Sedyaningsih E. R., et al. Three Indonesian clusters of H5N1 virus infection in 2005. N Engl J Med. 2006;355(21):2186–2194. doi: 10.1056/NEJMoa060930. [DOI] [PubMed] [Google Scholar]
  • 21.Normile D. Avian influenza. Human transmission but no pandemic in Indonesia. Science. 2006;312(5782):1855. doi: 10.1126/science.312.5782.1855b. [DOI] [PubMed] [Google Scholar]
  • 22.Li H., Yu K., Yang H., et al. Isolation and characterization of H5N1 and H9N2 influenza viruses from pigs in China (in Chinese) Chinese Journal of Preventive Veterinary Medicine. 2004;26(1):1–6. [Google Scholar]
  • 23.Zhu Q., Yang H., Chen W., et al. A naturally occurring deletion in its NS gene contributes to the attenuation of an H5N1 swine influenza virus in chickens. J Virol. 2008;82(1):220–228. doi: 10.1128/JVI.00978-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24.Kuiken T., Rimmelzwaan G., van Riel D., et al. Avian H5N1 influenza in cats. Science. 2004;306(5694):241. doi: 10.1126/science.1102287. [DOI] [PubMed] [Google Scholar]
  • 25.Desvaux S., Marx N., Ong S., et al. Highly pathogenic avian influenza virus (H5N1) outbreak in captive wild birds and cats, Cambodia. Emerg Infect Dis. 2009;15(3):475–478. doi: 10.3201/eid1503.081410. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 26.Keawcharoen J., Oraveerakul K., Kuiken T., et al. Avian influenza H5N1 in tigers and leopards. Emerg Infect Dis. 2004;10(12):2189–2191. doi: 10.3201/eid1012.040759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27.Thanawongnuwech R., Amonsin A., Tantilertcharoen R., et al. Probable tiger-to-tiger transmission of avian influenza H5N1. Emerg Infect Dis. 2005;11(5):699–701. doi: 10.3201/eid1105.050007. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 28.Songserm T., Amonsin A., Jam-on R., et al. Fatal avian influenza A H5N1 in a dog. Emerg Infect Dis. 2006;12(11):1744–1747. doi: 10.3201/eid1211.060542. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 29.Klopfleisch R., Wolf P. U., Wolf C., et al. Encephalitis in a stone marten (Martes foina) after natural infection with highly pathogenic avian influenza virus subtype H5N1. J Comp Pathol. 2007;137(2–3):155–159. doi: 10.1016/j.jcpa.2007.06.001. [DOI] [PubMed] [Google Scholar]
  • 30.Song X, Xiao H, Huang Y, et al. Serological surveillance of influenza A virus infection in Swine populations in Fujian Province, China: No evidence of naturally occurring H5N1 infection in pigs. Zoonoses and Public Health, 2009: in press [DOI] [PubMed]
  • 31.Hirst G. K. The Agglutination of red cells by allantoic fluid of chick embryos infected with influenza virus. Science. 1941;94(2427):22–23. doi: 10.1126/science.94.2427.22. [DOI] [PubMed] [Google Scholar]
  • 32.Gottschalk A. Neuraminidase: the specific enzyme of influenza virus and Vibrio cholerae. Biochim Biophys Acta. 1957;23(3):645–646. doi: 10.1016/0006-3002(57)90389-x. [DOI] [PubMed] [Google Scholar]
  • 33.Schauer R. Achievements and challenges of sialic acid research. Glycoconj J. 2000;17(7–9):485–499. doi: 10.1023/A:1011062223612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 34.Harduin-Lepers A., Mollicone R., Delannoy P., et al. The animal sialyltransferases and sialyltransferase-related genes: a phylogenetic approach. Glycobiology. 2005;15(8):805–817. doi: 10.1093/glycob/cwi063. [DOI] [PubMed] [Google Scholar]
  • 35.Suzuki Y. Sialobiology of influenza: molecular mechanism of host range variation of influenza viruses. Biol Pharm Bull. 2005;28(3):399–408. doi: 10.1248/bpb.28.399. [DOI] [PubMed] [Google Scholar]
  • 36.Ito T., Suzuki Y., Mitnaul L., et al. Receptor specificity of influenza A viruses correlates with the agglutination of erythrocytes from different animal species. Virology. 1997;227(2):493–499. doi: 10.1006/viro.1996.8323. [DOI] [PubMed] [Google Scholar]
  • 37.Ito T., Suzuki Y., Takada A., et al. Differences in sialic acid-galactose linkages in the chicken egg amnion and allantois influence human influenza virus receptor specificity and variant selection. J Virol. 1997;71(4):3357–3362. doi: 10.1128/jvi.71.4.3357-3362.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38.Suzuki Y., Ito T., Suzuki T., et al. Sialic acid species as a determinant of the host range of influenza A viruses. J Virol. 2000;74(24):11825–11831. doi: 10.1128/jvi.74.24.11825-11831.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 39.Parrish C. R., Kawaoka Y. The origins of new pandemic viruses: the acquisition of new host ranges by canine parvovirus and influenza A viruses. Annu Rev Microbiol. 2005;59:553–586. doi: 10.1146/annurev.micro.59.030804.121059. [DOI] [PubMed] [Google Scholar]
  • 40.Shinya K., Ebina M., Yamada S., et al. Avian flu: influenza virus receptors in the human airway. Nature. 2006;440(7083):435–436. doi: 10.1038/440435a. [DOI] [PubMed] [Google Scholar]
  • 41.van Riel D., Munster V. J., de Wit E., et al. H5N1 virus attachment to lower respiratory tract. Science. 2006;312(5772):399. doi: 10.1126/science.1125548. [DOI] [PubMed] [Google Scholar]
  • 42.Rogers G. N., Paulson J. C., Daniels R. S., et al. Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity. Nature. 1983;304(5921):76–78. doi: 10.1038/304076a0. [DOI] [PubMed] [Google Scholar]
  • 43.Naeve C. W., Hinshaw V. S., Webster R. G. Mutations in the hemagglutinin receptor-binding site can change the biological properties of an influenza virus. J Virol. 1984;51(2):567–569. doi: 10.1128/jvi.51.2.567-569.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 44.Connor R. J., Kawaoka Y., Webster R. G., et al. Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates. Virology. 1994;205(1):17–23. doi: 10.1006/viro.1994.1615. [DOI] [PubMed] [Google Scholar]
  • 45.Stevens J., Blixt O., Tumpey T. M., et al. Structure and receptor specificity of the hemagglutinin from an H5N1 influenza virus. Science. 2006;312(5772):404–410. doi: 10.1126/science.1124513. [DOI] [PubMed] [Google Scholar]
  • 46.Yamada S., Suzuki Y., Suzuki T., et al. Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors. Nature. 2006;444(7117):378–382. doi: 10.1038/nature05264. [DOI] [PubMed] [Google Scholar]
  • 47.Ha Y., Stevens D. J., Skehel J. J., et al. X-ray structures of H5 avian and H9 swine influenza virus hemagglutinins bound to avian and human receptor analogs. Proc Natl Acad Sci USA. 2001;98(20):11181–11186. doi: 10.1073/pnas.201401198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 48.Ito T., Couceiro J. N., Kelm S., et al. Molecular basis for the generation in pigs of influenza A viruses with pandemic potential. J Virol. 1998;72(9):7367–7373. doi: 10.1128/jvi.72.9.7367-7373.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 49.Van Reeth K. Avian and swine influenza viruses: our current understanding of the zoonotic risk. Vet Res. 2007;38(2):243–260. doi: 10.1051/vetres:2006062. [DOI] [PubMed] [Google Scholar]
  • 50.Shi W. F., Gibbs M. J., Zhang Y. Z., et al. Genetic analysis of four porcine avian influenza viruses isolated from Shandong, China. Arch Virol. 2008;153(1):211–217. doi: 10.1007/s00705-007-1083-1. [DOI] [PubMed] [Google Scholar]
  • 51.Choi Y. K., Nguyen T. D., Ozaki H., et al. Studies of H5N1 influenza virus infection of pigs by using viruses isolated in Vietnam and Thailand in 2004. J Virol. 2005;79(16):10821–10825. doi: 10.1128/JVI.79.16.10821-10825.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52.Jung K., Song D. S., Kang B. K., et al. Serologic surveillance of swine H1 and H3 and avian H5 and H9 influenza A virus infections in swine population in Korea. Prev Vet Med. 2007;79(2–4):294–303. doi: 10.1016/j.prevetmed.2006.12.005. [DOI] [PubMed] [Google Scholar]
  • 53.Lipatov A S, Kwon Y, Sarmento L, et al. Domestic pigs have low susceptibility to H5N1 highly pathogenic avian influenza viruses. PLoS Pathog. 2008;4(7):e1000102. doi: 10.1371/journal.ppat.1000102. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 54.Horimoto T., Kawaoka Y. Influenza: lessons from past pandemics, warnings from current incidents. Nat Rev Microbiol. 2005;3(8):591–600. doi: 10.1038/nrmicro1208. [DOI] [PubMed] [Google Scholar]
  • 55.Duan L., Bahl J., Smith G. J., et al. The development and genetic diversity of H5N1 influenza virus in China, 1996–2006. Virology. 2008;380(2):243–254. doi: 10.1016/j.virol.2008.07.038. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 56.Guan Y., Peiris J. S., Lipatov A. S., et al. Emergence of multiple genotypes of H5N1 avian influenza viruses in Hong Kong SAR. Proc Natl Acad Sci USA. 2002;99(13):8950–8955. doi: 10.1073/pnas.132268999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 57.Li K. S., Guan Y., Wang J., et al. Genesis of a highly pathogenic and potentially pandemic H5N1 influenza virus in eastern Asia. Nature. 2004;430(6996):209–213. doi: 10.1038/nature02746. [DOI] [PubMed] [Google Scholar]
  • 58.Chen H., Smith G. J., Li K. S., et al. Establishment of multiple subline-ages of H5N1 influenza virus in Asia: implications for pandemic control. Proc Natl Acad Sci USA. 2006;103(8):2845–2850. doi: 10.1073/pnas.0511120103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 59.Campitelli L., Ciccozzi M., Salemi M., et al. H5N1 influenza virus evolution: a comparison of different epidemics in birds and humans (1997–2004) J Gen Virol. 2006;87(Pt4):955–960. doi: 10.1099/vir.0.81397-0. [DOI] [PubMed] [Google Scholar]
  • 60.Kaverin N. V., Rudneva I. A., Ilyushina N. A., et al. Structure of antigenic sites on the haemagglutinin molecule of H5 avian influenza virus and phenotypic variation of escape mutants. J Gen Virol. 2002;83(Pt10):2497–2505. doi: 10.1099/0022-1317-83-10-2497. [DOI] [PubMed] [Google Scholar]
  • 61.Lee C. W., Senne D. A., Suarez D. L. Effect of vaccine use in the evolution of Mexican lineage H5N2 avian influenza virus. J Virol. 2004;78(15):8372–8381. doi: 10.1128/JVI.78.15.8372-8381.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 62.Suzuki Y. Natural selection on the influenza virus genome. Mol Biol Evol. 2006;23(10):1902–1911. doi: 10.1093/molbev/msl050. [DOI] [PubMed] [Google Scholar]
  • 63.Almond J. W. A single gene determines the host range of influenza virus. Nature. 1977;270(5638):617–618. doi: 10.1038/270617a0. [DOI] [PubMed] [Google Scholar]
  • 64.Subbarao E. K., London W., Murphy B. R. A single amino acid in the PB2 gene of influenza A virus is a determinant of host range. J Virol. 1993;67(4):1761–1764. doi: 10.1128/jvi.67.4.1761-1764.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 65.Hatta M., Gao P., Halfmann P., et al. Molecular basis for high virulence of Hong Kong H5N1 influenza A viruses. Science. 2001;293(5536):1840–1842. doi: 10.1126/science.1062882. [DOI] [PubMed] [Google Scholar]
  • 66.Palese P., Tobita K., Ueda M., et al. Characterization of temperature sensitive influenza virus mutants defective in neuraminidase. Virology. 1974;61(2):397–410. doi: 10.1016/0042-6822(74)90276-1. [DOI] [PubMed] [Google Scholar]
  • 67.Luo G., Chung J., Palese P. Alterations of the stalk of the influenza virus neuraminidase: deletions and insertions. Virus Res. 1993;29(2):141–153. doi: 10.1016/0168-1702(93)90055-r. [DOI] [PubMed] [Google Scholar]
  • 68.Castrucci M. R., Kawaoka Y. Biologic importance of neuraminidase stalk length in influenza A virus. J Virol. 1993;67(2):759–764. doi: 10.1128/jvi.67.2.759-764.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 69.Mitnaul L. J., Matrosovich M. N., Castrucci M. R., et al. Balanced hemagglutinin and neuraminidase activities are critical for efficient replication of influenza A virus. J Virol. 2000;74(13):6015–6020. doi: 10.1128/jvi.74.13.6015-6020.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 70.Wagner R., Matrosovich M., Klenk H. D. Functional balance between haemagglutinin and neuraminidase in influenza virus infections. Rev Med Virol. 2002;12(3):159–166. doi: 10.1002/rmv.352. [DOI] [PubMed] [Google Scholar]
  • 71.Garcia-Sastre A. Inhibition of interferon-mediated antiviral responses by influenza A viruses and other negative-strand RNA viruses. Virology. 2001;279(2):375–384. doi: 10.1006/viro.2000.0756. [DOI] [PubMed] [Google Scholar]
  • 72.Katze M. G., He Y., Gale M., Jr Viruses and interferon: a fight for supremacy. Nat Rev Immunol. 2002;2(9):675–687. doi: 10.1038/nri888. [DOI] [PubMed] [Google Scholar]
  • 73.Lee D. C., Cheung C. Y., Law A. H., et al. p38 mitogen-activated protein kinase-dependent hyperinduction of tumor necrosis factor alpha expression in response to avian influenza virus H5N1. J Virol. 2005;79(16):10147–10154. doi: 10.1128/JVI.79.16.10147-10154.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 74.To K. F., Chan P. K., Chan K. F., et al. Pathology of fatal human infection associated with avian influenza A H5N1 virus. J Med Virol. 2001;63(3):242–246. doi: 10.1002/1096-9071(200103)63:3<242::aid-jmv1007>3.0.co;2-n. [DOI] [PubMed] [Google Scholar]
  • 75.Huarte M., Sanz-Ezquerro J. J., Roncal F., et al. PA subunit from influenza virus polymerase complex interacts with a cellular protein with homology to a family of transcriptional activators. J Virol. 2001;75(18):8597–8604. doi: 10.1128/JVI.75.18.8597-8604.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 76.Deng T., Engelhardt O. G., Thomas B., et al. Role of ran binding protein 5 in nuclear import and assembly of the influenza virus RNA polymerase complex. J Virol. 2006;80(24):11911–11919. doi: 10.1128/JVI.01565-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 77.Honda A., Okamoto T., Ishihama A. Host factor Ebp1: selective inhibitor of influenza virus transcriptase. Genes Cells. 2007;12(2):133–142. doi: 10.1111/j.1365-2443.2007.01047.x. [DOI] [PubMed] [Google Scholar]
  • 78.O’Neill R. E., Palese P. NPI-1, the human homolog of SRP-1, interacts with influenza virus nucleoprotein. Virology. 1995;206(1):116–125. doi: 10.1016/s0042-6822(95)80026-3. [DOI] [PubMed] [Google Scholar]
  • 79.Wang P., Palese P., O’Neill R. E. The NPI-1/NPI-3 (karyopherin alpha) binding site on the influenza a virus nucleoprotein NP is a nonconventional nuclear localization signal. J Virol. 1997;71(3):1850–1856. doi: 10.1128/jvi.71.3.1850-1856.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 80.Momose F., Basler C. F., O’Neill R. E., et al. Cellular splicing factor RAF-2p48/NPI-5/BAT1/UAP56 interacts with the influenza virus nucleoprotein and enhances viral RNA synthesis. J Virol. 2001;75(4):1899–1908. doi: 10.1128/JVI.75.4.1899-1908.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 81.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. doi: 10.1093/emboj/19.24.6751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 82.Hirayama E., Atagi H., Hiraki A., et al. Heat shock protein 70 is related to thermal inhibition of nuclear export of the influenza virus ribonucleoprotein complex. J Virol. 2004;78(3):1263–1270. doi: 10.1128/JVI.78.3.1263-1270.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 83.Mayer D., Molawi K., Martinez-Sobrido L., et al. Identification of cellular interaction partners of the influenza virus ribonucleoprotein complex and polymerase complex using proteomic-based approaches. J Proteome Res. 2007;6(2):672–682. doi: 10.1021/pr060432u. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 84.Jorba N., Juarez S., Torreira E., et al. Analysis of the interaction of influenza virus polymerase complex with human cell factors. Proteomics. 2008;8(10):2077–2088. doi: 10.1002/pmic.200700508. [DOI] [PubMed] [Google Scholar]
  • 85.Watanabe K., Handa H., Mizumoto K., et al. Mechanism for inhibition of influenza virus RNA polymerase activity by matrix protein. J Virol. 1996;70(1):241–247. doi: 10.1128/jvi.70.1.241-247.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 86.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(1):288–296. doi: 10.1093/emboj/17.1.288. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 87.Watanabe K., Takizawa N., Katoh M., et al. Inhibition of nuclear export of ribonucleoprotein complexes of influenza virus by leptomycin B. Virus Res. 2001;77(1):31–42. doi: 10.1016/s0168-1702(01)00263-5. [DOI] [PubMed] [Google Scholar]
  • 88.Zhirnov O. P., Klenk H. D. Histones as a target for influenza virus matrix protein M1. Virology. 1997;235(2):302–310. doi: 10.1006/viro.1997.8700. [DOI] [PubMed] [Google Scholar]
  • 89.Pleschka S., Wolff T., Ehrhardt C., et al. Influenza virus propagation is impaired by inhibition of the Raf/MEK/ERK signalling cascade. Nat Cell Biol. 2001;3(3):301–305. doi: 10.1038/35060098. [DOI] [PubMed] [Google Scholar]
  • 90.Reinhardt J., Wolff T. The influenza A virus M1 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. doi: 10.1016/s0378-1135(00)00169-3. [DOI] [PubMed] [Google Scholar]
  • 91.Watanabe K., Fuse T., Asanoa I., et al. Identification of Hsc70 as an influenza virus matrix protein (M1) binding factor involved in the virus life cycle. FEBS Letters. 2006;580(24):5785–5790. doi: 10.1016/j.febslet.2006.09.040. [DOI] [PubMed] [Google Scholar]
  • 92.Zhirnov O. P., Ksenofontov A. L., Kuzmina S. G., et al. Interaction of influenza A virus M1 matrix protein with caspases. Biochemistry-Moscow. 2002;67(5):534–539. doi: 10.1023/a:1015542110798. [DOI] [PubMed] [Google Scholar]
  • 93.Liu X, Sun P L, Yu M, et al. Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication. Cell Microbiol. 2009, doi: 10.1111/j.1462-5822.2009.01286.x [DOI] [PubMed]
  • 94.Nemeroff M. E., Barabino S. M., Li Y., et al. 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. doi: 10.1016/s1097-2765(00)80099-4. [DOI] [PubMed] [Google Scholar]
  • 95.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 relocalized in the nuclei of infected cells. J Virol. 1998;72(9):7170–7180. doi: 10.1128/jvi.72.9.7170-7180.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 96.Chen Z., Li Y., Krug R. M. Influenza A virus NS1 protein targets poly(A)-binding protein II of the cellular 3′-end processing machinery. EMBO J. 1999;18(8):2273–2283. doi: 10.1093/emboj/18.8.2273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 97.Falcon A. M., Fortes P., Marion R. M., et al. Interaction of influenza virus NS1 protein and the human homologue of Staufen in vivo and in vitro. Nucleic acids research. 1999;27(11):2241–2247. doi: 10.1093/nar/27.11.2241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 98.Burgui I., Aragon T., Ortin J., et al. PABP1 and eIF4GI associate with influenza virus NS1 protein in viral mRNA translation initiation complexes. J Gen Virol. 2003;84(Pt12):3263–3274. doi: 10.1099/vir.0.19487-0. [DOI] [PubMed] [Google Scholar]
  • 99.Samuel C. E. Antiviral actions of interferons. Clin Microbiol Rev. 2001;14(4):778–809. doi: 10.1128/CMR.14.4.778-809.2001. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 100.Wang X. Y., Hinson E. R., Cresswell P. The interferon-inducible protein viperin inhibits influenza virus release by perturbing lipid rafts. Cell Host Microbe. 2007;2(2):96–105. doi: 10.1016/j.chom.2007.06.009. [DOI] [PubMed] [Google Scholar]
  • 101.Chin K. C., Cresswell P. Viperin (cig5), an IFN-inducible antiviral protein directly induced by human cytomegalovirus. Proc Natl Acad Sci USA. 2001;98(26):15125–15130. doi: 10.1073/pnas.011593298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 102.Turan K., Mibayashi M., Sugiyama K., et al. Nuclear MxA proteins form a complex with influenza virus NP and inhibit the transcription of the engineered influenza virus genome. Nucleic Acids Res. 2004;32(2):643–652. doi: 10.1093/nar/gkh192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 103.Hale B. G., Randall R. E., Ortin J., et al. The multifunctional NS1 protein of influenza A viruses. J Gen Virol. 2008;89(Pt10):2359–2376. doi: 10.1099/vir.0.2008/004606-0. [DOI] [PubMed] [Google Scholar]
  • 104.Goodman A. G., Smith J. A., Balachandran S., et al. The cellular protein P58IPK regulates influenza virus mRNA translation and replication through a PKR-mediated mechanism. J Virol. 2007;81(5):2221–2230. doi: 10.1128/JVI.02151-06. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Science in China. Series C, Life Sciences are provided here courtesy of Nature Publishing Group

RESOURCES