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TitleHuman monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins.
Journal, issue, pagesPLoS Pathog, Vol. 15, Issue 11, Page e1008061, Year 2019
Publish dateNov 7, 2019
AuthorsJose A Quiroz / Ryan J Malonis / Larissa B Thackray / Courtney A Cohen / Jesper Pallesen / Rohit K Jangra / Rebecca S Brown / Daniel Hofmann / Frederick W Holtsberg / Sergey Shulenin / Elisabeth K Nyakatura / Lorellin A Durnell / Vinayak Rayannavar / Johanna P Daily / Andrew B Ward / M Javad Aman / John M Dye / Kartik Chandran / Michael S Diamond / Margaret Kielian / Jonathan R Lai /
PubMed AbstractChikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal ...Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus that causes persistent arthritis in a subset of human patients. We report the isolation and functional characterization of monoclonal antibodies (mAbs) from two patients infected with CHIKV in the Dominican Republic. Single B cell sorting yielded a panel of 46 human mAbs of diverse germline lineages that targeted epitopes within the E1 or E2 glycoproteins. MAbs that recognized either E1 or E2 proteins exhibited neutralizing activity. Viral escape mutations localized the binding epitopes for two E1 mAbs to sites within domain I or the linker between domains I and III; and for two E2 mAbs between the β-connector region and the B-domain. Two of the E2-specific mAbs conferred protection in vivo in a stringent lethal challenge mouse model of CHIKV infection, whereas the E1 mAbs did not. These results provide insight into human antibody response to CHIKV and identify candidate mAbs for therapeutic intervention.
External linksPLoS Pathog / PubMed:31697791 / PubMed Central
MethodsEM (single particle)
Resolution21.0 - 24.0 Å
Structure data

EMDB-20268:
Chikungunya virus p62/E1 complex
Method: EM (single particle) / Resolution: 21.0 Å

EMDB-20269:
Chikungunya virus p62/E1 in complex with Fab from IgG DC2.271B
Method: EM (single particle) / Resolution: 24.0 Å

Source
  • Chikungunya virus
  • Homo sapiens (human)

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