1887

Abstract

The M1 protein is a major structural protein that has multiple functions in various steps within the life cycle of the influenza A virus (IAV). However, little is currently known about the role of M1 in IAV replication and the associated pathogenesis. In this study, six isogenic H1N1 WSN33 viruses, constructed to express unique M1 proteins derived from various strains, subtypes or WSN33 itself, were tested to determine and functional exchangeability of M1 proteins in the replication and pathogenesis of the WSN33 virus. Despite five chimeric M1 viruses replicating to levels similar to those of the parental WSN33 virus in cell cultures, all M1 chimeras exhibited improved replication and enhanced virulence in mice when compared with the WSN33 virus. Interestingly, M1 proteins derived from swine viruses caused more severe clinical diseases than those from human or quail. These data indicate that the M1 protein is an important determinant of viral replication and pathogenic properties in mice, although the functions of M1 observed are not adequately reflected in simple infections of cultured cells. Chimeric M1 viruses that are variable in their clinical manifestations described here will aid future understanding of the role of M1 in IAV pathogenesis.

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2013-04-01
2022-01-26
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References

  1. Akarsu H., Burmeister W. P., Petosa C., Petit I., Müller C. W., Ruigrok R. W., Baudin F. 2003; Crystal structure of the M1 protein-binding domain of the influenza A virus nuclear export protein (NEP/NS2). EMBO J 22:4646–4655 [View Article][PubMed]
    [Google Scholar]
  2. Ali A., Avalos R. T., Ponimaskin E., Nayak D. P. 2000; Influenza virus assembly: effect of influenza virus glycoproteins on the membrane association of M1 protein. J Virol 74:8709–8719 [View Article][PubMed]
    [Google Scholar]
  3. Avalos R. T., Yu Z., Nayak D. P. 1997; Association of influenza virus NP and M1 proteins with cellular cytoskeletal elements in influenza virus-infected cells. J Virol 71:2947–2958[PubMed]
    [Google Scholar]
  4. Baudin F., Petit I., Weissenhorn W., Ruigrok R. W. 2001; In vitro dissection of the membrane and RNP binding activities of influenza virus M1 protein. Virology 281:102–108 [View Article][PubMed]
    [Google Scholar]
  5. Black B. L., Rhodes R. B., McKenzie M., Lyles D. S. 1993; The role of vesicular stomatitis virus matrix protein in inhibition of host-directed gene expression is genetically separable from its function in virus assembly. J Virol 67:4814–4821[PubMed]
    [Google Scholar]
  6. Brown E. G., Liu H., Kit L. C., Baird S., Nesrallah M. 2001; Pattern of mutation in the genome of influenza A virus on adaptation to increased virulence in the mouse lung: identification of functional themes. Proc Natl Acad Sci U S A 98:6883–6888 [View Article][PubMed]
    [Google Scholar]
  7. Bucher D., Popple S., Baer M., Mikhail A., Gong Y. F., Whitaker C., Paoletti E., Judd A. 1989; M protein (M1) of influenza virus: antigenic analysis and intracellular localization with monoclonal antibodies. J Virol 63:3622–3633[PubMed]
    [Google Scholar]
  8. Buckler-White A. J., Naeve C. W., Murphy B. R. 1986; Characterization of a gene coding for M proteins which is involved in host range restriction of an avian influenza A virus in monkeys. J Virol 57:697–700[PubMed]
    [Google Scholar]
  9. Bui M., Whittaker G., Helenius A. 1996; Effect of M1 protein and low pH on nuclear transport of influenza virus ribonucleoproteins. J Virol 70:8391–8401[PubMed]
    [Google Scholar]
  10. Bui M., Wills E. G., Helenius A., Whittaker G. R. 2000; Role of the influenza virus M1 protein in nuclear export of viral ribonucleoproteins. J Virol 74:1781–1786 [View Article][PubMed]
    [Google Scholar]
  11. Burleigh L. M., Calder L. J., Skehel J. J., Steinhauer D. A. 2005; Influenza a viruses with mutations in the m1 helix six domain display a wide variety of morphological phenotypes. J Virol 79:1262–1270 [View Article][PubMed]
    [Google Scholar]
  12. Calder L. J., Wasilewski S., Berriman J. A., Rosenthal P. B. 2010; Structural organization of a filamentous influenza A virus. Proc Natl Acad Sci U S A 107:10685–10690 [View Article][PubMed]
    [Google Scholar]
  13. Cao S., Liu X., Yu M., Li J., Jia X., Bi Y., Sun L., Gao G. F., Liu W. 2012; A nuclear export signal in the matrix protein of Influenza A virus is required for efficient virus replication. J Virol 86:4883–4891 [View Article][PubMed]
    [Google Scholar]
  14. Chen C., Li F., Montelaro R. C. 2001; Functional roles of equine infectious anemia virus Gag p9 in viral budding and infection. J Virol 75:9762–9770 [View Article][PubMed]
    [Google Scholar]
  15. Chen B. J., Leser G. P., Morita E., Lamb R. A. 2007; Influenza virus hemagglutinin and neuraminidase, but not the matrix protein, are required for assembly and budding of plasmid-derived virus-like particles. J Virol 81:7111–7123 [View Article][PubMed]
    [Google Scholar]
  16. Chen B. J., Leser G. P., Jackson D., Lamb R. A. 2008; The influenza virus M2 protein cytoplasmic tail interacts with the M1 protein and influences virus assembly at the site of virus budding. J Virol 82:10059–10070 [View Article][PubMed]
    [Google Scholar]
  17. Chou Y. Y., Albrecht R. A., Pica N., Lowen A. C., Richt J. A., García-Sastre A., Palese P., Hai R. 2011; The M segment of the 2009 new pandemic H1N1 influenza virus is critical for its high transmission efficiency in the guinea pig model. J Virol 85:11235–11241 [View Article][PubMed]
    [Google Scholar]
  18. Das S. C., Watanabe S., Hatta M., Noda T., Neumann G., Ozawa M., Kawaoka Y. 2012; The highly conserved arginine residues at positions 76 through 78 of influenza A virus matrix protein M1 play an important role in viral replication by affecting the intracellular localization of M1. J Virol 86:1522–1530 [View Article][PubMed]
    [Google Scholar]
  19. Demirov D., Gabriel G., Schneider C., Hohenberg H., Ludwig S. 2012; Interaction of influenza A virus matrix protein with RACK1 is required for virus release. Cell Microbiol 14:774–789 [View Article][PubMed]
    [Google Scholar]
  20. Ducatez M. F., Hause B., Stigger-Rosser E., Darnell D., Corzo C., Juleen K., Simonson R., Brockwell-Staats C., Rubrum A.other authors 2011; Multiple reassortment between pandemic (H1N1) 2009 and endemic influenza viruses in pigs, United States. Emerg Infect Dis 17:1624–1629 [View Article][PubMed]
    [Google Scholar]
  21. Elleman C. J., Barclay W. S. 2004; The M1 matrix protein controls the filamentous phenotype of influenza A virus. Virology 321:144–153 [View Article][PubMed]
    [Google Scholar]
  22. Elster C., Larsen K., Gagnon J., Ruigrok R. W., Baudin F. 1997; Influenza virus M1 protein binds to RNA through its nuclear localization signal. J Gen Virol 78:1589–1596[PubMed]
    [Google Scholar]
  23. Elton D., Simpson-Holley M., Archer K., Medcalf L., Hallam R., McCauley J., Digard P. 2001; Interaction of the influenza virus nucleoprotein with the cellular CRM1-mediated nuclear export pathway. J Virol 75:408–419 [View Article][PubMed]
    [Google Scholar]
  24. Enami K., Sato T. A., Nakada S., Enami M. 1994; Influenza virus NS1 protein stimulates translation of the M1 protein. J Virol 68:1432–1437[PubMed]
    [Google Scholar]
  25. Fan S., Deng G., Song J., Tian G., Suo Y., Jiang Y., Guan Y., Bu Z., Kawaoka Y., Chen H. 2009; Two amino acid residues in the matrix protein M1 contribute to the virulence difference of H5N1 avian influenza viruses in mice. Virology 384:28–32 [View Article][PubMed]
    [Google Scholar]
  26. Faul E. J., Lyles D. S., Schnell M. J. 2009; Interferon response and viral evasion by members of the family Rhabdoviridae. Viruses 1:832–851 [View Article][PubMed]
    [Google Scholar]
  27. Fontana J., Cardone G., Heymann J. B., Winkler D. C., Steven A. C. 2012; Structural changes in Influenza virus at low pH characterized by cryo-electron tomography. J Virol 86:2919–2929 [View Article][PubMed]
    [Google Scholar]
  28. Furuse Y., Suzuki A., Kamigaki T., Oshitani H. 2009; Evolution of the M gene of the influenza A virus in different host species: large-scale sequence analysis. Virol J 6:67 [View Article][PubMed]
    [Google Scholar]
  29. Garcia C. C., Russo R. C., Guabiraba R., Fagundes C. T., Polidoro R. B., Tavares L. P., Salgado A. P., Cassali G. D., Sousa L. P.other authors 2010; Platelet-activating factor receptor plays a role in lung injury and death caused by Influenza A in mice. PLoS Pathog 6:e1001171 [View Article][PubMed]
    [Google Scholar]
  30. Govorkova E. A., Gambaryan A. S., Claas E. C., Smirnov Y. A. 2000; Amino acid changes in the hemagglutinin and matrix proteins of influenza A (H2) viruses adapted to mice. Acta Virol 44:241–248[PubMed]
    [Google Scholar]
  31. Harris A., Forouhar F., Qiu S., Sha B., Luo M. 2001; The crystal structure of the influenza matrix protein M1 at neutral pH: M1-M1 protein interfaces can rotate in the oligomeric structures of M1. Virology 289:34–44 [View Article][PubMed]
    [Google Scholar]
  32. Hirayama E., Atagi H., Hiraki A., Kim J. 2004; Heat shock protein 70 is related to thermal inhibition of nuclear export of the influenza virus ribonucleoprotein complex. J Virol 78:1263–1270 [View Article][PubMed]
    [Google Scholar]
  33. Hoffmann E., Neumann G., Hobom G., Webster R. G., Kawaoka Y. 2000a; “Ambisense” approach for the generation of influenza A virus: vRNA and mRNA synthesis from one template. Virology 267:310–317 [View Article][PubMed]
    [Google Scholar]
  34. Hoffmann E., Neumann G., Kawaoka Y., Hobom G., Webster R. G. 2000b; A DNA transfection system for generation of influenza A virus from eight plasmids. Proc Natl Acad Sci U S A 97:6108–6113 [View Article][PubMed]
    [Google Scholar]
  35. Huang S., Chen J., Wang H., Sun B., Wang H., Zhang Z., Zhang X., Chen Z. 2009; Influenza A virus matrix protein 1 interacts with hTFIIIC102-s, a short isoform of the polypeptide 3 subunit of human general transcription factor IIIC. Arch Virol 154:1101–1110 [View Article][PubMed]
    [Google Scholar]
  36. Hui E. K., Smee D. F., Wong M. H., Nayak D. P. 2006; Mutations in influenza virus M1 CCHH, the putative zinc finger motif, cause attenuation in mice and protect mice against lethal influenza virus infection. J Virol 80:5697–5707 [View Article][PubMed]
    [Google Scholar]
  37. Lam T. T., Hon C. C., Pybus O. G., Kosakovsky Pond S. L., Wong R. T., Yip C. W., Zeng F., Leung F. C. 2008; Evolutionary and transmission dynamics of reassortant H5N1 influenza virus in Indonesia. PLoS Pathog 4:e1000130 [View Article][PubMed]
    [Google Scholar]
  38. Lee K. H., Youn J. W., Kim H. J., Seong B. L. 2001; Identification and characterization of mutations in the high growth vaccine strain of influenza virus. Arch Virol 146:369–377 [View Article][PubMed]
    [Google Scholar]
  39. Li F., Chen C., Puffer B. A., Montelaro R. C. 2002; Functional replacement and positional dependence of homologous and heterologous L domains in equine infectious anemia virus replication. J Virol 76:1569–1577 [View Article][PubMed]
    [Google Scholar]
  40. Liu Q., Qiao C., Marjuki H., Bawa B., Ma J., Guillossou S., Webby R. J., Richt J. A., Ma W. 2011; Combination of PB2 271A and SR polymorphism at positions 590/591 is critical for viral replication and virulence of swine influenza virus in cultured cells and in vivo. J Virol 86:1233–1237 [View Article][PubMed]
    [Google Scholar]
  41. Liu X., Sun L., Yu M., Wang Z., Xu C., Xue Q., Zhang K., Ye X., Kitamura Y., Liu W. 2009; Cyclophilin A interacts with influenza A virus M1 protein and impairs the early stage of the viral replication. Cell Microbiol 11:730–741 [View Article][PubMed]
    [Google Scholar]
  42. Ma W., Liu Q., Bawa B., Qiao C., Qi W., Shen H., Chen Y., Ma J., Li X.other authors 2012; The neuraminidase and matrix genes of the 2009 pandemic influenza H1N1 virus cooperate functionally to facilitate efficient replication and transmissibility in pigs. J Gen Virol 93:1261–1268 [View Article][PubMed]
    [Google Scholar]
  43. Martin K., Helenius A. 1991a; Nuclear transport of influenza virus ribonucleoproteins: the viral matrix protein (M1) promotes export and inhibits import. Cell 67:117–130 [View Article][PubMed]
    [Google Scholar]
  44. Martin K., Helenius A. 1991b; Transport of incoming influenza virus nucleocapsids into the nucleus. J Virol 65:232–244[PubMed]
    [Google Scholar]
  45. McCullers J. A., Hoffmann E., Huber V. C., Nickerson A. D. 2005; A single amino acid change in the C-terminal domain of the matrix protein M1 of influenza B virus confers mouse adaptation and virulence. Virology 336:318–326 [View Article][PubMed]
    [Google Scholar]
  46. Murphy B. R., Buckler-White A. J., London W. T., Snyder M. H. 1989; Characterization of the M protein and nucleoprotein genes of an avian influenza A virus which are involved in host range restriction in monkeys. Vaccine 7:557–561 [View Article][PubMed]
    [Google Scholar]
  47. Nayak D. P., Balogun R. A., Yamada H., Zhou Z. H., Barman S. 2009; Influenza virus morphogenesis and budding. Virus Res 143:147–161 [View Article][PubMed]
    [Google Scholar]
  48. Neumann G., Hughes M. T., Kawaoka Y. 2000; Influenza A virus NS2 protein mediates vRNP nuclear export through NES-independent interaction with hCRM1. EMBO J 19:6751–6758 [View Article][PubMed]
    [Google Scholar]
  49. Noton S. L., Medcalf E., Fisher D., Mullin A. E., Elton D., Digard P. 2007; Identification of the domains of the influenza A virus M1 matrix protein required for NP binding, oligomerization and incorporation into virions. J Gen Virol 88:2280–2290 [View Article][PubMed]
    [Google Scholar]
  50. O’Neill R. E., Talon J., Palese P. 1998; The influenza virus NEP (NS2 protein) mediates the nuclear export of viral ribonucleoproteins. EMBO J 17:288–296 [View Article][PubMed]
    [Google Scholar]
  51. Okada A., Miura T., Takeuchi H. 2003; Zinc- and pH-dependent conformational transition in a putative interdomain linker region of the influenza virus matrix protein M1. Biochemistry 42:1978–1984 [View Article][PubMed]
    [Google Scholar]
  52. Pal S., Santos A., Rosas J. M., Ortiz-Guzman J., Rosas-Acosta G. 2011; Influenza A virus interacts extensively with the cellular SUMOylation system during infection. Virus Res 158:12–27 [View Article][PubMed]
    [Google Scholar]
  53. Palese P., Shaw M. 2007; Orthomyxoviridae: the viruses and their replication. In Field’s Virology, 5th edn. pp. 1647–1689 Edited by Fields B. N., Knipe D. M., Howley P. M. Philadelphia: Wolters Kluwer Health/Lippincott Williams & Wilkins;
    [Google Scholar]
  54. Perez D. R., Donis R. O. 1998; The matrix 1 protein of influenza A virus inhibits the transcriptase activity of a model influenza reporter genome in vivo. Virology 249:52–61 [View Article][PubMed]
    [Google Scholar]
  55. Reid A. H., Fanning T. G., Janczewski T. A., McCall S., Taubenberger J. K. 2002; Characterization of the 1918 “Spanish” influenza virus matrix gene segment. J Virol 76:10717–10723 [View Article][PubMed]
    [Google Scholar]
  56. Reinhardt J., Wolff T. 2000; 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 74:87–100 [View Article][PubMed]
    [Google Scholar]
  57. Richt J. A., Lager K. M., Janke B. H., Woods R. D., Webster R. G., Webby R. J. 2003; Pathogenic and antigenic properties of phylogenetically distinct reassortant H3N2 swine influenza viruses cocirculating in the United States. J Clin Microbiol 41:3198–3205 [View Article][PubMed]
    [Google Scholar]
  58. Roberts P. C., Lamb R. A., Compans R. W. 1998; The M1 and M2 proteins of influenza A virus are important determinants in filamentous particle formation. Virology 240:127–137 [View Article][PubMed]
    [Google Scholar]
  59. Rossman J. S., Lamb R. A. 2011; Influenza virus assembly and budding. Virology 411:229–236 [View Article][PubMed]
    [Google Scholar]
  60. Ruigrok R. W., Barge A., Durrer P., Brunner J., Ma K., Whittaker G. R. 2000; Membrane interaction of influenza virus M1 protein. Virology 267:289–298 [View Article][PubMed]
    [Google Scholar]
  61. Sheehan D. C., Hrapchak B. B. 1980; Nuclear and cytoplasmic staining. In Theory and Practice of Histotechnology pp. 137–159 Edited by Sheehan, D. C., Hrapchak, B. B., Columbus, O. H.: Battelle Press [View Article][PubMed]
    [Google Scholar]
  62. Wakefield L., Brownlee G. G. 1989; RNA-binding properties of influenza A virus matrix protein M1. Nucleic Acids Res 17:8569–8580 [View Article][PubMed]
    [Google Scholar]
  63. Wang D., Harmon A., Jin J., Francis D. H., Christopher-Hennings J., Nelson E., Montelaro R. C., Li F. 2010; The lack of an inherent membrane targeting signal is responsible for the failure of the matrix (M1) protein of influenza A virus to bud into virus-like particles. J Virol 84:4673–4681 [View Article][PubMed]
    [Google Scholar]
  64. Ward A. C. 1995; Specific changes in the M1 protein during adaptation of influenza virus to mouse. Arch Virol 140:383–389 [View Article][PubMed]
    [Google Scholar]
  65. Ward A. C. 1996; Neurovirulence of influenza A virus. J Neurovirol 2:139–151 [View Article][PubMed]
    [Google Scholar]
  66. Ward A. C. 1997; Virulence of influenza A virus for mouse lung. Virus Genes 14:187–194 [View Article][PubMed]
    [Google Scholar]
  67. Watanabe K., Handa H., Mizumoto K., Nagata K. 1996; Mechanism for inhibition of influenza virus RNA polymerase activity by matrix protein. J Virol 70:241–247[PubMed]
    [Google Scholar]
  68. Watanabe K., Fuse T., Asano I., Tsukahara F., Maru Y., Nagata K., Kitazato K., Kobayashi N. 2006; Identification of Hsc70 as an influenza virus matrix protein (M1) binding factor involved in the virus life cycle. FEBS Lett 580:5785–5790 [View Article][PubMed]
    [Google Scholar]
  69. Wu C. Y., Jeng K. S., Lai M. M. 2011; The SUMOylation of matrix protein M1 modulates the assembly and morphogenesis of influenza A virus. J Virol 85:6618–6628 [View Article][PubMed]
    [Google Scholar]
  70. Yasuda J., Nakada S., Kato A., Toyoda T., Ishihama A. 1993; Molecular assembly of influenza virus: association of the NS2 protein with virion matrix. Virology 196:249–255 [View Article][PubMed]
    [Google Scholar]
  71. Ye Z., Robinson D., Wagner R. R. 1995; Nucleus-targeting domain of the matrix protein (M1) of influenza virus. J Virol 69:1964–1970[PubMed]
    [Google Scholar]
  72. Ye Z., Liu T., Offringa D. P., McInnis J., Levandowski R. A. 1999; Association of influenza virus matrix protein with ribonucleoproteins. J Virol 73:7467–7473[PubMed]
    [Google Scholar]
  73. Zhao H., Ekström M., Garoff H. 1998; The M1 and NP proteins of influenza A virus form homo- but not heterooligomeric complexes when coexpressed in BHK-21 cells. J Gen Virol 79:2435–2446[PubMed]
    [Google Scholar]
  74. Zhirnov O. P. 1992; Isolation of matrix protein M1 from influenza viruses by acid-dependent extraction with nonionic detergent. Virology 186:324–330 [View Article][PubMed]
    [Google Scholar]
  75. Zhirnov O. P., Klenk H. D. 1997; Histones as a target for influenza virus matrix protein M1. Virology 235:302–310 [View Article][PubMed]
    [Google Scholar]
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