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-Structure paper
タイトル | Neutralizing antibodies protect mice against Venezuelan equine encephalitis virus aerosol challenge. |
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ジャーナル・号・ページ | J Exp Med, Vol. 219, Issue 4, Year 2022 |
掲載日 | 2022年4月4日 |
著者 | Natasha M Kafai / Lauren E Williamson / Elad Binshtein / Soila Sukupolvi-Petty / Christina L Gardner / Jaclyn Liu / Samantha Mackin / Arthur S Kim / Nurgun Kose / Robert H Carnahan / Ana Jung / Lindsay Droit / Douglas S Reed / Scott A Handley / William B Klimstra / James E Crowe / Michael S Diamond / |
PubMed 要旨 | Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing ...Venezuelan equine encephalitis virus (VEEV) remains a risk for epidemic emergence or use as an aerosolized bioweapon. To develop possible countermeasures, we isolated VEEV-specific neutralizing monoclonal antibodies (mAbs) from mice and a human immunized with attenuated VEEV strains. Functional assays and epitope mapping established that potently inhibitory anti-VEEV mAbs bind distinct antigenic sites in the A or B domains of the E2 glycoprotein and block multiple steps in the viral replication cycle including attachment, fusion, and egress. A 3.2-Å cryo-electron microscopy reconstruction of VEEV virus-like particles bound by a human Fab suggests that antibody engagement of the B domain may result in cross-linking of neighboring spikes to prevent conformational requirements for viral fusion. Prophylaxis or postexposure therapy with these mAbs protected mice against lethal aerosol challenge with VEEV. Our study defines functional and structural mechanisms of mAb protection and suggests that multiple antigenic determinants on VEEV can be targeted for vaccine or antibody-based therapeutic development. |
リンク | J Exp Med / PubMed:35297953 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.2 - 4.2 Å |
構造データ | EMDB-25102, PDB-7sfu: EMDB-25103, PDB-7sfv: EMDB-25104, PDB-7sfw: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | VIRUS / VLP / VEEV / viral protein / VIRUS/IMMUNE SYSTEM / fab / VIRUS-IMMUNE SYSTEM complex |