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TitleCryo-EM Structures of Eastern Equine Encephalitis Virus Reveal Mechanisms of Virus Disassembly and Antibody Neutralization.
Journal, issue, pagesCell Rep, Vol. 25, Issue 11, Page 3136-33147.e5, Year 2018
Publish dateDec 11, 2018
AuthorsS 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 AbstractAlphaviruses 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 linksCell Rep / PubMed:30540945 / PubMed Central
MethodsEM (single particle)
Resolution4.4 - 8.2 Å
Structure data

9249

6mui

EMDB-9249, PDB-6mui:
CryoEM structure of chimeric Eastern Equine Encephalitis Virus with Fab of EEEV-42 antibody
Method: EM (single particle) / Resolution: 7.7 Å

9274

6mw9

EMDB-9274, PDB-6mw9:
CryoEM structure of chimeric Eastern Equine Encephalitis Virus with Fab of EEEV-3 antibody
Method: EM (single particle) / Resolution: 7.3 Å

9275

6mwc

EMDB-9275, PDB-6mwc:
CryoEM structure of chimeric Eastern Equine Encephalitis Virus with Fab of EEEV-5 antibody
Method: EM (single particle) / Resolution: 7.5 Å

9278

6mwv

EMDB-9278, PDB-6mwv:
CryoEM structure of Chimeric Eastern Equine Encephalitis Virus with Fab of EEEV-58 Antibody
Method: EM (single particle) / Resolution: 7.3 Å

9279

6mwx

EMDB-9279, PDB-6mwx:
CryoEM structure of Chimeric Eastern Equine Encephalitis Virus with Fab of EEEV-69 Antibody
Method: EM (single particle) / Resolution: 8.2 Å

9280

6mx4

EMDB-9280, PDB-6mx4:
CryoEM structure of chimeric Eastern Equine Encephalitis Virus
Method: EM (single particle) / Resolution: 4.4 Å

9281

6mx7

EMDB-9281, PDB-6mx7:
CryoEM structure of chimeric Eastern Equine Encephalitis Virus: Genome-Binding Capsid N-terminal Domain
Method: EM (single particle) / Resolution: 4.8 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose / N-Acetylglucosamine

Source
  • mus musculus (house mouse)
  • EEEV (virus)
  • Mouse (mice)
  • eastern equine encephalitis virus
KeywordsVIRUS/IMMUNE SYSTEM / Alphavirus / EEEV / Eastern Equine Encephalitis Virus / Sindbis / Fab / VIRUS-IMMUNE SYSTEM complex / VIRUS

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