Asymmetric structure of the influenza A virus and novel function of the matrix protein M1

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Abstract

Influenza virus is an enveloped virus. It comprises two major modules: external lipoprotein envelope and internal ribonucleoprotein (RNP) containing the genomic negative-strand RNA. Lipoprotein envelope contains four vital proteins: hemagglutinin (HA), neuraminidase (NA), transmembrane ionic channel M2, and minor amounts of nuclear export protein NEP. RNP contains RNA and four polypeptides: major nucleocapsid protein NP and three polymerase subunits PB1, PB2, PA. Both modules are linked with each other by matrix M1 maintaining the virus integrity. According to the structural function, NP and M1 are predominant in virus particle in the amounts of 1000 and 3000 molecules, respectively. In addition to the structural function, M1 plays a role in regulation of intracellular and nuclear migration of viral RNP and virus assembly, referred as budding process, at the plasma membrane in infected cells. The bipolar structure of the influenza virus characterized by asymmetric location of RNP and nonregular distribution of M1 and M2 inside the virion is reviewed. The role of M1 in maintaining the asymmetric structure of the virus particle and regulation of RNP transport inside virus particle is considered. First experimental data confirming (i) intravirion RNP transport and its outside exit directed by the M1 and (ii) the importance of this process in virus uncoating and initiation of infection in target cell are discussed. A novel class of antiviral agents activating ATP-ase of the early endosome compartment in the target cell is discussed.

About the authors

O. P. Zhirnov

Virology «Federal Research Centre of Epidemiology and Microbiology named after the honorary academician N.F. Gamaleya»

Author for correspondence.
Email: zhirnov@inbox.ru
Russian Federation

References

  1. Жирнов О.П., Букринская А.Г. Белки вируса гриппа. Включение вновь синтезированных вирусных белков в вирионы. Вопросы вирусологии. 1982; (5): 549-56.
  2. Жирнов О.П., Маныкин А.А. рН-зависимые перестройки в структуре вируса гриппа А. Вопросы вирусологии. 2014; 59 (3): 41-6.
  3. Жирнов О.П. Белки вируса гриппа: солюбилизация in vitro матриксного белка М1 вириона зависит от протеолитического нарезания гемагглютинина и от рН. В кн.: Каверин Н.В., ред. Молекулярная биология и генетическая инженерия вирусов. М.; 1989: 50-7.
  4. Kilbourne E.D., Murphy J.S. Genetic studies of influenza viruses. I. Viral morphology and growth capacity as exchangeable genetic traits. Rapid in ovo adaptation of early passage Asian strain isolates by combination with PR8. J. Exp. Med. 1960; 111: 387-406.
  5. Roberts P.C., Lamb R.A., Compans R.W. The M1 and M2 proteins of influenza A virus are important determinants in filamentous particle formation. Virology. 1998; 240 (1): 127-37.
  6. McCown M.F., Pekosz A. The influenza A virus M2 cytoplasmic tail is required for infectious virus production and efficient genome packaging. J. Virol. 2005; 79 (6): 3595-605.
  7. Iwatsuki-Horimoto K., Horimoto T., Noda T., Kiso M., Maeda J., Watanabe S. et al. The cytoplasmic tail of the influenza A virus M2 protein plays a role in viral assembly. J. Virol. 2006; 80 (11): 5233-40.
  8. Elleman C.J., Barclay W.S. The M1 matrix protein controls the filamentous phenotype of influenza A virus. Virology. 2004; 321 (1): 144-53.
  9. Roberts K.L., Leser G.P., Ma C., Lamb R.A. The amphipathic helix of influenza a virus M2 protein is required for filamentous bud formation and scission of filamentous and spherical particles. J. Virol. 2013; 87 (18): 9973-82.
  10. Bruce E.A., Digard P., Stuart A.D. The Rab11 pathway is required for influenza A virus budding and filament formation. J. Virol. 2010; 84 (12): 5848-59.
  11. Choppin P.W., Murphy J.S., Tamm I. Studies of two kinds of virus particles which comprise influenza A2 virus strains. III. Morphological characteristics: independence to morphological and functional traits. J. Exp. Med. 1960; 112: 945-52.
  12. McHardy A.C., Adams B. The role of genomics in tracking the evolution of influenza A virus. PLoS Pathog. 2009; 5 (10): e1000566.
  13. Eisfeld A.J., Neumann G., Kawaoka Y. At the centre: influenza A virus ribonucleoproteins. Nat. Rev. Microbiol. 2015; 13 (1): 28-41.
  14. Zhirnov O.P., Klenk H.D., Wright P.F. Aprotinin and similar protease inhibitors as drugs against influenza. Antiviral. Res. 2011; 92 (1): 27-36.
  15. Zhirnov O.P., Manykin A.A. Abnormal morphological vesicles in influenza a virus exposed to acid pH. Bull. Exp. Biol .Med. 2015; 158 (6): 776-80.
  16. Pinto L.H., Lamb R.A. The M2 proton channels of influenza A and B viruses. J. Biol. Chem. 2006; 281 (14): 8997-9000.
  17. Zhirnov O.P. Solubilization of matrix protein M1/M from virions occurs at different pH for orthomyxo- and paramyxoviruses. Virology. 1990; 176 (1): 274-9.
  18. Zhirnov O.P. Isolation of matrix protein M1 from influenza viruses by acid-dependent extraction with nonionic detergent. Virology. 1992; 186 (1): 324-30.
  19. Yasuda J., Nakada S., Kato A., Toyoda T., Ishihama A. Molecular assembly of influenza virus: association of the NS2 protein with virion matrix. Virology. 1993; 196 (1): 249-55.
  20. Noda T., Sugita Y., Aoyama K., Hirase A., Kawakami E., Miyazawa A. et al. Three-dimensional analysis of ribonucleoprotein complexes in influenza A virus. Nat. Commun. 2012; 3: 639.
  21. Nayak D.P., Balogun R.A., Yamada H., Zhou Z.H., Barman S. Influenza virus morphogenesis and budding. Virus Res. 2009; 143 (2): 147-61.
  22. Rossman J.S., Lamb R.A. Influenza virus assembly and budding. Virology. 2011; 411 (2): 229-36.
  23. Rossman J.S., Jing X., Leser G.P., Lamb R.A. Influenza virus M2 protein mediates ESCRT-independent membrane scission. Cell. 2010; 142 (6): 902-13.
  24. Harris A., Cardone G., Winkler D.C., Heymann J.B., Brecher M., White J.M. et al. Influenza virus pleiomorphy characterized by cryoelectron tomography. Proc. Natl. Acad. Sci. U S A. 2006; 103 (50): 19123-7.
  25. Barman S., Nayak D.P. Lipid raft disruption by cholesterol depletion enhances influenza A virus budding from MDCK cells. J. Virol. 2007; 81 (22): 12 169-78.
  26. Ali A., Avalos R.T., Ponimaskin E., Nayak D.P. Influenza virus assembly: effect of influenza virus glycoproteins on the membrane association of M1 protein. J. Virol. 2000; 74 (18): 8709-19.
  27. Helenius A. Unpacking the incoming influenza virus. Cell. 1992; 69 (4): 577-8.
  28. Sieczkarski S.B., Whittaker G.R. Influenza virus can enter and infect cells in the absence of clathrin-mediated endocytosis. J. Virol. 2002; 76 (20): 10 455-64.
  29. Stauffer S., Feng Y., Nebioglu F., Heilig R., Picotti P., Helenius A. Stepwise priming by acidic pH and a high K+ concentration is required for efficient uncoating of influenza A virus cores after penetration. J. Virol. 2014; 88 (22): 13 029-46.
  30. Akira S., Uematsu S., Takeuchi O. Pathogen recognition and innate immunity. Cell. 2006; 124 (4): 783-801.
  31. Moore C.B., Ting J.P. Regulation of mitochondrial antiviral signaling pathways. Immunity. 2008; 28 (6): 735-9.

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