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TitleStructural Basis of Zika Virus Specific Neutralization in Subsequent Flavivirus Infections.
Journal, issue, pagesViruses, Vol. 12, Issue 12, Year 2020
Publish dateNov 24, 2020
AuthorsMadhumati Sevvana / Thomas F Rogers / Andrew S Miller / Feng Long / Thomas Klose / Nathan Beutler / Yen-Chung Lai / Mara Parren / Laura M Walker / Geeta Buda / Dennis R Burton / Michael G Rossmann / Richard J Kuhn /
PubMed AbstractZika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We ...Zika virus (ZIKV), a mosquito-borne human flavivirus that causes microcephaly and other neurological disorders, has been a recent focus for the development of flavivirus vaccines and therapeutics. We report here a 4.0 Å resolution structure of the mature ZIKV in complex with ADI-30056, a ZIKV-specific human monoclonal antibody (hMAb) isolated from a ZIKV infected donor with a prior dengue virus infection. The structure shows that the hMAb interactions span across the E protein dimers on the virus surface, inhibiting conformational changes required for the formation of infectious fusogenic trimers similar to the hMAb, ZIKV-117. Structure-based functional analysis, and structure and sequence comparisons, identified ZIKV residues essential for neutralization and crucial for the evolution of highly potent E protein crosslinking Abs in ZIKV. Thus, this epitope, ZIKV's "Achilles heel", defined by the contacts between ZIKV and ADI-30056, could be a suitable target for the design of therapeutic antibodies.
External linksViruses / PubMed:33255202 / PubMed Central
MethodsEM (single particle)
Resolution4.0 Å
Structure data

22818

7kcr

EMDB-22818, PDB-7kcr:
Cryo-EM structure of Zika virus in complex with E protein cross-linking human monoclonal antibody ADI30056
Method: EM (single particle) / Resolution: 4.0 Å

Source
  • homo sapiens (human)
  • zika virus zikv/h. sapiens/frenchpolynesia/10087pf/2013
KeywordsVIRUS/IMMUNE SYSTEM / Zika Virus / Flavivirus / Zika-Antibody / VIRUS-IMMUNE SYSTEM complex

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