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-Structure paper
タイトル | Human monoclonal antibodies against chikungunya virus target multiple distinct epitopes in the E1 and E2 glycoproteins. |
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ジャーナル・号・ページ | PLoS Pathog, Vol. 15, Issue 11, Page e1008061, Year 2019 |
掲載日 | 2019年11月7日 |
![]() | Jose 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 要旨 | 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 ...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. |
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手法 | EM (単粒子) |
解像度 | 21.0 - 24.0 Å |
構造データ | ![]() EMDB-20268: ![]() EMDB-20269: |
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