1887

Abstract

Human rhinovirus is the causative agent of the common cold and belongs to the non-enveloped picornavirus family. A trigger such as receptor binding or low pH initiates conformational changes in the capsid that allow the virus to attach to membranes and form a pore for the translocation of viral RNA into the cytoplasm. We previously showed that recombinant capsid protein VP4 was able to form membrane pores. In this study, we show the N-terminus but not C-terminus of VP4 formed pores with properties similar to full-length VP4 and consistent with the size required for transfer of RNA. Sera against the N-terminus but not C-terminus of VP4 were shown to neutralize virus infectivity. Together, this suggests that the N-terminus of VP4 is responsible for membrane activity. This study contributes to an improved understanding of the mechanisms for involvement of VP4 in entry and its potential as an antiviral target.

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2016-12-16
2019-09-18
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References

  1. Abrams C. C., King A. M., Belsham G. J..( 1995;). Assembly of foot-and-mouth disease virus empty capsids synthesized by a vaccinia virus expression system. . J Gen Virol 76: 3089–3098. [CrossRef] [PubMed]
    [Google Scholar]
  2. Bubeck D., Filman D. J., Cheng N., Steven A. C., Hogle J. M., Belnap D. M..( 2005;). The structure of the poliovirus 135S cell entry intermediate at 10-angstrom resolution reveals the location of an externalized polypeptide that binds to membranes. . J Virol 79: 7745–7755. [CrossRef] [PubMed]
    [Google Scholar]
  3. Butan C., Filman D. J., Hogle J. M..( 2014;). Cryo-electron microscopy reconstruction shows poliovirus 135S particles poised for membrane interaction and RNA release. . J Virol 88: 1758–1770. [CrossRef] [PubMed]
    [Google Scholar]
  4. Davis M. P., Bottley G., Beales L. P., Killington R. A., Rowlands D. J., Tuthill T. J..( 2008;). Recombinant VP4 of human rhinovirus induces permeability in model membranes. . J Virol 82: 4169–4174. [CrossRef] [PubMed]
    [Google Scholar]
  5. Fricks C. E., Hogle J. M..( 1990;). Cell-induced conformational change in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding. . J Virol 64: 1934–1945.[PubMed]
    [Google Scholar]
  6. Goodwin S., Tuthill T. J., Arias A., Killington R. A., Rowlands D. J..( 2009;). Foot-and-mouth disease virus assembly: processing of recombinant capsid precursor by exogenous protease induces self-assembly of pentamers in vitro in a myristoylation-dependent manner. . J Virol 83: 11275–11282. [CrossRef] [PubMed]
    [Google Scholar]
  7. Hadfield A. T., Lee W., Zhao R., Oliveira M. A., Minor I., Rueckert R. R., Rossmann M. G..( 1997;). The refined structure of human rhinovirus 16 at 2.15 Å resolution: implications for the viral life cycle. . Structure 5: 427–441. [CrossRef] [PubMed]
    [Google Scholar]
  8. Jacobs S. E., Lamson D. M., St George K., Walsh T. J..( 2013;). Human rhinoviruses. . Clin Microbiol Rev 26: 135–162. [CrossRef] [PubMed]
    [Google Scholar]
  9. Katpally U., Fu T. M., Freed D. C., Casimiro D. R., Smith T. J..( 2009;). Antibodies to the buried N terminus of rhinovirus VP4 exhibit cross-serotypic neutralization. . J Virol 83: 7040–7048. [CrossRef] [PubMed]
    [Google Scholar]
  10. Li Q., Yafal A. G., Lee Y. M., Hogle J., Chow M..( 1994;). Poliovirus neutralization by antibodies to internal epitopes of VP4 and VP1 results from reversible exposure of these sequences at physiological temperature. . J Virol 68: 3965–3970.[PubMed]
    [Google Scholar]
  11. Lin J., Lee L. Y., Roivainen M., Filman D. J., Hogle J. M., Belnap D. M..( 2012;). Structure of the Fab-labeled ‘breathing’ state of native poliovirus. . J Virol 86: 5959–5962. [CrossRef] [PubMed]
    [Google Scholar]
  12. Marc D., Drugeon G., Haenni A. L., Girard M., van der Werf S..( 1989;). Role of myristoylation of poliovirus capsid protein VP4 as determined by site-directed mutagenesis of its N-terminal sequence. . EMBO J 8: 2661–2668.[PubMed]
    [Google Scholar]
  13. Moscufo N., Simons J., Chow M..( 1991;). Myristoylation is important at multiple stages in poliovirus assembly. . J Virol 65: 2372–2380.[PubMed]
    [Google Scholar]
  14. Moscufo N., Chow M..( 1992;). Myristate-protein interactions in poliovirus: interactions of VP4 threonine 28 contribute to the structural conformation of assembly intermediates and the stability of assembled virions. . J Virol 66: 6849–6857.[PubMed]
    [Google Scholar]
  15. Panjwani A., Strauss M., Gold S., Wenham H., Jackson T., Chou J. J., Rowlands D. J., Stonehouse N. J., Hogle J. M., Tuthill T. J..( 2014;). Capsid protein VP4 of human rhinovirus induces membrane permeability by the formation of a size-selective multimeric pore. . PLoS Pathog 10: e1004294. [CrossRef] [PubMed]
    [Google Scholar]
  16. Ren J., Wang X., Hu Z., Gao Q., Sun Y., Li X., Porta C., Walter T. S., Gilbert R. J. et al.( 2013;). Picornavirus uncoating intermediate captured in atomic detail. . Nat Commun 4: 1929. [CrossRef] [PubMed]
    [Google Scholar]
  17. Rweyemamu M. M..( 1984;). Antigenic variation in foot-and-mouth disease: studies based on the virus neutralization reaction. . J Biol Stand 12: 323–337.[PubMed] [CrossRef]
    [Google Scholar]
  18. Sabanathan S., Tan L. V., Thwaites L., Wills B., Qui P. T., Rogier van Doorn H..( 2014;). Enterovirus 71 related severe hand, foot and mouth disease outbreaks in South-East Asia: current situation and ongoing challenges. . J Epidemiol Community Health 68: 500–502. [CrossRef] [PubMed]
    [Google Scholar]
  19. Strauss M., Levy H. C., Bostina M., Filman D. J., Hogle J. M..( 2013;). RNA transfer from poliovirus 135S particles across membranes is mediated by long umbilical connectors. . J Virol 87: 3903–3914. [CrossRef] [PubMed]
    [Google Scholar]
  20. Tuthill T. J., Bubeck D., Rowlands D. J., Hogle J. M..( 2006;). Characterization of early steps in the poliovirus infection process: receptor-decorated liposomes induce conversion of the virus to membrane-anchored entry-intermediate particles. . J Virol 80: 172–180. [CrossRef] [PubMed]
    [Google Scholar]
  21. Wang X., Peng W., Ren J., Hu Z., Xu J., Lou Z., Li X., Yin W., Shen X. et al.( 2012;). A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71. . Nat Struct Mol Biol 19: 424–429. [CrossRef] [PubMed]
    [Google Scholar]
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