Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.

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TitleCryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.
Publication TypeJournal Article
Year of Publication2018
AuthorsS Hasan, S, Sun, C, Kim, AS, Watanabe, Y, Chen, C-L, Klose, T, Buda, G, Crispin, M, Diamond, MS, Klimstra, WB, Rossmann, MG
JournalCell Rep
Volume25
Issue11
Pagination3136-3147.e5
Date Published2018 12 11
ISSN2211-1247
KeywordsAnimals, Antibodies, Monoclonal, Antibodies, Neutralizing, Antibodies, Viral, Binding Sites, Capsid Proteins, Cell Line, Tumor, Cryoelectron Microscopy, Encephalitis Virus, Eastern Equine, Glycosylation, Heparitin Sulfate, Humans, Integrins, Models, Molecular, Neutralization Tests, Protein Multimerization, Static Electricity, Virus Assembly
Abstract

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.

DOI10.1016/j.celrep.2018.11.067
Alternate JournalCell Rep
PubMed ID30540945
PubMed Central IDPMC6302666
Grant ListR01 AI095366 / AI / NIAID NIH HHS / United States
R01 AI095436 / AI / NIAID NIH HHS / United States
R21 AI117331 / AI / NIAID NIH HHS / United States