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Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.
Hasan, S Saif; Sun, Chengqun; Kim, Arthur S; Watanabe, Yasunori; Chen, Chun-Liang; Klose, Thomas; Buda, Geeta; Crispin, Max; Diamond, Michael S; Klimstra, William B; Rossmann, Michael G.
Afiliação
  • Hasan SS; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
  • Sun C; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Kim AS; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Watanabe Y; Centre for Biological Sciences and Institute of Life Sciences, University of Southampton, Southampton SO17 1BJ, UK; Oxford Glycobiology Institute, Department of Biochemistry, University of Oxford, Oxford OX1 3QU, UK; Division of Structural Biology, University of Oxford, Oxford OX3 7BN, UK.
  • Chen CL; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
  • Klose T; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
  • Buda G; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
  • Crispin M; Centre for Biological Sciences and Institute of Life Sciences, University of Southampton, Southampton SO17 1BJ, UK.
  • Diamond MS; Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO 63110,
  • Klimstra WB; Department of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USA.
  • Rossmann MG; Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA. Electronic address: mr@purdue.edu.
Cell Rep ; 25(11): 3136-3147.e5, 2018 12 11.
Article em En | MEDLINE | ID: mdl-30540945
Alphaviruses are enveloped pathogens that cause arthritis and encephalitis. Here, we report a 4.4-Å cryoelectron microscopy (cryo-EM) structure of eastern equine encephalitis virus (EEEV), an alphavirus that causes fatal encephalitis in humans. Our analysis provides insights into viral entry into host cells. The envelope protein E2 showed a binding site for the cellular attachment factor heparan sulfate. The presence of a cryptic E2 glycan suggests how EEEV escapes surveillance by lectin-expressing myeloid lineage cells, which are sentinels of the immune system. A mechanism for nucleocapsid core release and disassembly upon viral entry was inferred based on pH changes and capsid dissociation from envelope proteins. The EEEV capsid structure showed a viral RNA genome binding site adjacent to a ribosome binding site for viral genome translation following genome release. Using five Fab-EEEV complexes derived from neutralizing antibodies, our investigation provides insights into EEEV host cell interactions and protective epitopes relevant to vaccine design.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Testes de Neutralização / Montagem de Vírus / Microscopia Crioeletrônica / Vírus da Encefalite Equina do Leste / Anticorpos Antivirais Idioma: En Ano de publicação: 2018 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Testes de Neutralização / Montagem de Vírus / Microscopia Crioeletrônica / Vírus da Encefalite Equina do Leste / Anticorpos Antivirais Idioma: En Ano de publicação: 2018 Tipo de documento: Article