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Title | Cryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization. |
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Journal, issue, pages | Cell Rep, Vol. 25, Issue 11, Page 3136-33147.e5, Year 2018 |
Publish date | Dec 11, 2018 |
Authors | 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 / |
PubMed 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 ...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. |
External links | Cell Rep / PubMed:30540945 / PubMed Central |
Methods | EM (single particle) |
Resolution | 4.4 - 8.2 Å |
Structure data | EMDB-9249, PDB-6mui: EMDB-9274, PDB-6mw9: EMDB-9275, PDB-6mwc: EMDB-9278, PDB-6mwv: EMDB-9279, PDB-6mwx: |
Chemicals | ChemComp-NAG: |
Source |
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Keywords | VIRUS/IMMUNE SYSTEM / Alphavirus / EEEV / Eastern Equine Encephalitis Virus / Sindbis / Fab / VIRUS-IMMUNE SYSTEM complex / VIRUS |