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TitleStructural basis of a potent human monoclonal antibody against Zika virus targeting a quaternary epitope.
Journal, issue, pagesProc Natl Acad Sci U S A, Vol. 116, Issue 5, Page 1591-1596, Year 2019
Publish dateJan 29, 2019
AuthorsFeng Long / Michael Doyle / Estefania Fernandez / Andrew S Miller / Thomas Klose / Madhumati Sevvana / Aubrey Bryan / Edgar Davidson / Benjamin J Doranz / Richard J Kuhn / Michael S Diamond / James E Crowe / Michael G Rossmann /
PubMed AbstractZika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and ...Zika virus (ZIKV) is a major human pathogen and member of the genus in the Flaviviridae family. In contrast to most other insect-transmitted flaviviruses, ZIKV also can be transmitted sexually and from mother to fetus in humans. During recent outbreaks, ZIKV infections have been linked to microcephaly, congenital disease, and Guillain-Barré syndrome. Neutralizing antibodies have potential as therapeutic agents. We report here a 4-Å-resolution cryo-electron microscopy structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195. The footprint of the ZIKV-195 Fab fragment expands across two adjacent envelope (E) protein protomers. ZIKV neutralization by this antibody is presumably accomplished by cross-linking the E proteins, which likely prevents formation of E protein trimers required for fusion of the viral and cellular membranes. A single dose of ZIKV-195 administered 5 days after virus inoculation showed marked protection against lethality in a stringent mouse model of infection.
External linksProc Natl Acad Sci U S A / PubMed:30642974 / PubMed Central
MethodsEM (single particle)
Resolution4.0 Å
Structure data

9131

6mid

EMDB-9131, PDB-6mid:
Cryo-EM structure of the ZIKV virion in complex with Fab fragments of the potently neutralizing human monoclonal antibody ZIKV-195
Method: EM (single particle) / Resolution: 4.0 Å

Source
  • homo sapiens (human)
  • zika virus (isolate zikv/human/french polynesia/10087pf/2013)
KeywordsVIRUS/IMMUNE SYSTEM / virus / monoclonal antibody / complex / VIRUS-IMMUNE SYSTEM complex

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