A sensor-adaptor mechanism for enterovirus uncoating from structures of EV71

Enterovirus 71 (EV71) is a major agent of hand, foot and mouth disease in children that can cause severe central nervous system disease and death. No vaccine or antiviral therapy is available. High-resolution structural analysis of the mature virus and natural empty particles shows that the mature virus is structurally similar to other enteroviruses. In contrast, the empty particles are markedly expanded and resemble elusive enterovirus-uncoating intermediates not previously characterized in atomic detail. Hydrophobic pockets in the EV71 capsid are collapsed in this expanded particle, providing a detailed explanation of the mechanism for receptor-binding triggered virus uncoating. These structures provide a model for enterovirus uncoating in which the VP1 GH loop acts as an adaptor-sensor for cellular receptor attachment, converting heterologous inputs to a generic uncoating mechanism, highlighting new opportunities for therapeutic intervention.

[1]  P. Thompson,et al.  Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus. , 1996, The EMBO journal.

[2]  R J Read,et al.  Crystallography & NMR system: A new software suite for macromolecular structure determination. , 1998, Acta crystallographica. Section D, Biological crystallography.

[3]  P. McMinn.  An overview of the evolution of enterovirus 71 and its clinical and public health significance. , 2002, FEMS microbiology reviews.

[4]  G. L. Le Bouvier.  The modification of poliovirus antigens by heat and ultraviolet light. , 1955, Lancet.

[5]  R. Eisenberg,et al.  Two Distinct Binding Affinities of Poliovirus for Its Cellular Receptor* , 2000, The Journal of Biological Chemistry.

[6]  Z. Rao,et al.  Structures of EV71 RNA-dependent RNA polymerase in complex with substrate and analogue provide a drug target against the hand-foot-and-mouth disease pandemic in China , 2010, Protein & Cell.

[7]  S. Koike,et al.  Scavenger receptor B2 is a cellular receptor for enterovirus 71 , 2009, Nature Medicine.

[8]  L. Philipson,et al.  Specific Alterations of Coxsackievirus B3 Eluted from Hela Cells , 1971, Journal of virology.

[9]  S. Curry,et al.  Dissecting the roles of VP0 cleavage and RNA packaging in picornavirus capsid stabilization: the structure of empty capsids of foot-and-mouth disease virus , 1997, Journal of virology.

[10]  John E. Johnson,et al.  Structure of a human common cold virus and functional relationship to other picornaviruses , 1985, Nature.

[11]  M. Rossmann,et al.  Picornavirus-receptor interactions. , 2002, Trends in microbiology.

[12]  David I. Stuart,et al.  A procedure for setting up high-throughput nanolitre crystallization experiments. II. Crystallization results , 2003 .

[13]  Alasdair C. Steven,et al.  The Structure of the Poliovirus 135S Cell Entry Intermediate at 10-Angstrom Resolution Reveals the Location of an Externalized Polypeptide That Binds to Membranes , 2005, Journal of Virology.

[14]  D I Stuart,et al.  Crystal structure of cat muscle pyruvate kinase at a resolution of 2.6 A. , 1979, Journal of molecular biology.

[15]  G. Bricogne,et al.  Refinement of severely incomplete structures with maximum likelihood in BUSTER-TNT. , 2004, Acta crystallographica. Section D, Biological crystallography.

[16]  Zbyszek Otwinowski,et al.  Diffraction data analysis in the presence of radiation damage , 2010, Acta crystallographica. Section D, Biological crystallography.

[17]  M. Shimojima,et al.  Human P-selectin glycoprotein ligand-1 is a functional receptor for enterovirus 71 , 2009, Nature Medicine.

[18]  D. Filman,et al.  Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: Structure of the empty capsid assembly intermediate at 2.9 Å resolution , 1994, Protein Science.

[19]  Shu-Pei Lien,et al.  Identification and characterization of a cross-neutralization epitope of Enterovirus 71. , 2011, Vaccine.

[20]  E. Wimmer,et al.  The crystal structure of coxsackievirus A21 and its interaction with ICAM-1. , 2005, Structure.

[21]  Lester G. Carter,et al.  A procedure for setting up high‐throughput nanolitre crystallization experiments. Crystallization workflow for initial screening, automated storage, imaging and optimization , 2005, Acta crystallographica. Section D, Biological crystallography.

[22]  M. Rossmann,et al.  Conformational variability of a picornavirus capsid: pH-dependent structural changes of Mengo virus related to its host receptor attachment site and disassembly. , 1990, Virology.

[23]  P. Vogt,et al.  Cell entry by non-enveloped viruses. , 2010, Current topics in microbiology and immunology.

[24]  R. Rueckert,et al.  The structure of human rhinovirus 16. , 1993, Structure.

[25]  D. Stuart,et al.  The crystal structure of coxsackievirus A9: new insights into the uncoating mechanisms of enteroviruses. , 1999, Structure.

[26]  Jorge Navaza,et al.  UROX 2.0: an interactive tool for fitting atomic models into electron-microscopy reconstructions , 2009, Acta crystallographica. Section D, Biological crystallography.

[27]  V. Chow,et al.  Identification of neutralizing linear epitopes from the VP1 capsid protein of Enterovirus 71 using synthetic peptides. , 2007, Virus research.

[28]  D. Filman,et al.  Structural factors that control conformational transitions and serotype specificity in type 3 poliovirus. , 1989, The EMBO journal.

[29]  Gwyndaf Evans,et al.  In situ macromolecular crystallography using microbeams , 2012, Acta crystallographica. Section D, Biological crystallography.

[30]  E. Wimmer,et al.  Complexes of Poliovirus Serotypes with Their Common Cellular Receptor, CD155 , 2003, Journal of Virology.

[31]  D. Neubauer,et al.  Picornaviruses , 1990, Current Topics in Microbiology and Immunology.

[32]  D. Baltimore,et al.  A plasma membrane component able to bind and alter virions of poliovirus type 1: studies on cell-free alteration using a simplified assay. , 1977, Virology.

[33]  D. Stuart,et al.  Implications for viral uncoating from the structure of bovine enterovirus , 1995, Nature Structural Biology.

[34]  J. Hogle,et al.  Cell-induced conformational change in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding , 1990, Journal of virology.

[35]  H. Eggers,et al.  Inhibition of uncoating of poliovirus by arildone, a new antiviral drug. , 1979, Virology.

[36]  V. Racaniello.  Early events in poliovirus infection: virus-receptor interactions. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[37]  K. Lonberg-Holm,et al.  Early alteration of poliovirus in infected cells and its specific inhibition. , 1975, The Journal of general virology.

[38]  M. Pallansch,et al.  Complete nucleotide sequence of enterovirus 71 is distinct from poliovirus. , 1995, Virus research.

[39]  J. Hogle.  Poliovirus cell entry: common structural themes in viral cell entry pathways. , 2002, Annual review of microbiology.

[40]  Marc C. Morais,et al.  Crystal structure of CD155 and electron microscopic studies of its complexes with polioviruses , 2008, Proceedings of the National Academy of Sciences.

[41]  A. Pani,et al.  Poliovirus morphogenesis. I. Identification of 80S dissociable particles and evidence for the artifactual production of procapsids , 1981, Journal of virology.

[42]  M G Rossmann,et al.  Structure of a human rhinovirus complexed with its receptor molecule. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[43]  James M. Hogle,et al.  Catching a Virus in the Act of RNA Release: a Novel Poliovirus Uncoating Intermediate Characterized by Cryo-Electron Microscopy , 2010, Journal of Virology.

[44]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[45]  D. Baltimore,et al.  Morphogenesis of poliovirus. I. Association of the viral RNA with coat protein. , 1968, Journal of molecular biology.

[46]  James M. Hogle,et al.  Poliovirus RNA Is Released from the Capsid near a Twofold Symmetry Axis , 2010, Journal of Virology.

[47]  D. Filman,et al.  An Externalized Polypeptide Partitions between Two Distinct Sites on Genome-Released Poliovirus Particles , 2011, Journal of Virology.

[48]  R. Crainic,et al.  Detection by monoclonal antibodies of an antigenic determinant critical for poliovirus neutralization present on VP1 and on heat-inactivated virions. , 1983, Virology.

[49]  Alasdair C. Steven,et al.  Molecular Tectonic Model of Virus Structural Transitions: the Putative Cell Entry States of Poliovirus , 2000, Journal of Virology.

[50]  A. Mcclelland,et al.  Mechanisms of receptor-mediated rhinovirus neutralization defined by two soluble forms of ICAM-1 , 1991, Journal of virology.

[51]  C. Morrow,et al.  Amino acid substitutions in the poliovirus maturation cleavage site affect assembly and result in accumulation of provirions , 1995, Journal of virology.

[52]  R. A. Killington,et al.  Recombinant VP4 of Human Rhinovirus Induces Permeability in Model Membranes , 2008, Journal of Virology.

[53]  P. Chong,et al.  Purification and Characterization of Enterovirus 71 Viral Particles Produced from Vero Cells Grown in a Serum-Free Microcarrier Bioreactor System , 2011, PloS one.

[54]  P. Emsley,et al.  Features and development of Coot , 2010, Acta crystallographica. Section D, Biological crystallography.

[55]  James M. Hogle,et al.  Structures of poliovirus complexes with anti-viral drugs: implications for viral stability and drug design , 1994, Current Biology.

[56]  M. Sudol,et al.  The importance of being proline: the interaction of proline‐rich motifs in signaling proteins with their cognate domains , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[57]  G Vriend,et al.  The site of attachment in human rhinovirus 14 for antiviral agents that inhibit uncoating. , 1986, Science.

[58]  M. Ho,et al.  Annexin II Binds to Capsid Protein VP1 of Enterovirus 71 and Enhances Viral Infectivity , 2011, Journal of Virology.

[59]  M G Rossmann,et al.  Acid-induced structural changes in human rhinovirus 14: possible role in uncoating. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[60]  D S Moss,et al.  Main-chain bond lengths and bond angles in protein structures. , 1993, Journal of molecular biology.

[61]  D. Filman,et al.  Three-dimensional structure of poliovirus at 2.9 A resolution. , 1985, Science.