Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization
Summary: 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 entr...
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doaj-82e0eb4194f74d8897bc68aecf67e7ef2020-11-25T01:56:42ZengElsevierCell Reports2211-12472018-12-01251131363147.e5Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody NeutralizationS. Saif Hasan0Chengqun Sun1Arthur S. Kim2Yasunori Watanabe3Chun-Liang Chen4Thomas Klose5Geeta Buda6Max Crispin7Michael S. Diamond8William B. Klimstra9Michael G. Rossmann10Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment 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, USACentre 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, UKDepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USADepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USACentre for Biological Sciences and Institute of Life Sciences, University of Southampton, Southampton SO17 1BJ, UKDepartment 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, USA; The Andrew M. and Jane M. Bursky Center for Human Immunology and Immunotherapy Programs, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Immunology, University of Pittsburgh, Pittsburgh, PA 15261, USA; Center for Vaccine Research, University of Pittsburgh, Pittsburgh, PA 15261, USADepartment of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA; Corresponding authorSummary: 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. : Hasan et al. use single-particle cryoelectron microscopy to elucidate the molecular basis of host cell entry of neurovirulent EEEV. They show that the EEEV envelope is primed for intracellular pH sensing and subsequent disassembly. Monoclonal antibodies effectively inhibit EEEV entry by cross-linking the viral envelope. Keywords: alphavirus, cryoelectron microscopy, glycosylation, antibodies, conformational changes, virus entry, virus disassemblyhttp://www.sciencedirect.com/science/article/pii/S2211124718318436 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
S. Saif Hasan Chengqun Sun Arthur S. Kim Yasunori Watanabe Chun-Liang Chen Thomas Klose Geeta Buda Max Crispin Michael S. Diamond William B. Klimstra Michael G. Rossmann |
spellingShingle |
S. Saif Hasan Chengqun Sun Arthur S. Kim Yasunori Watanabe Chun-Liang Chen Thomas Klose Geeta Buda Max Crispin Michael S. Diamond William B. Klimstra Michael G. Rossmann Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization Cell Reports |
author_facet |
S. Saif Hasan Chengqun Sun Arthur S. Kim Yasunori Watanabe Chun-Liang Chen Thomas Klose Geeta Buda Max Crispin Michael S. Diamond William B. Klimstra Michael G. Rossmann |
author_sort |
S. Saif Hasan |
title |
Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization |
title_short |
Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization |
title_full |
Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization |
title_fullStr |
Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization |
title_full_unstemmed |
Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization |
title_sort |
cryo-em structures of eastern equine encephalitis virus reveal mechanisms of virus disassembly and antibody neutralization |
publisher |
Elsevier |
series |
Cell Reports |
issn |
2211-1247 |
publishDate |
2018-12-01 |
description |
Summary: 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. : Hasan et al. use single-particle cryoelectron microscopy to elucidate the molecular basis of host cell entry of neurovirulent EEEV. They show that the EEEV envelope is primed for intracellular pH sensing and subsequent disassembly. Monoclonal antibodies effectively inhibit EEEV entry by cross-linking the viral envelope. Keywords: alphavirus, cryoelectron microscopy, glycosylation, antibodies, conformational changes, virus entry, virus disassembly |
url |
http://www.sciencedirect.com/science/article/pii/S2211124718318436 |
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