+検索条件
-Structure paper
タイトル | Neutralizing Monoclonal Antibodies Block Chikungunya Virus Entry and Release by Targeting an Epitope Critical to Viral Pathogenesis. |
---|---|
ジャーナル・号・ページ | Cell Rep, Vol. 13, Issue 11, Page 2553-2564, Year 2015 |
掲載日 | 2015年12月22日 |
著者 | Jing Jin / Nathan M Liss / Dong-Hua Chen / Maofu Liao / Julie M Fox / Raeann M Shimak / Rachel H Fong / Daniel Chafets / Sonia Bakkour / Sheila Keating / Marina E Fomin / Marcus O Muench / Michael B Sherman / Benjamin J Doranz / Michael S Diamond / Graham Simmons / |
PubMed 要旨 | We evaluated the mechanism by which neutralizing human monoclonal antibodies inhibit chikungunya virus (CHIKV) infection. Potently neutralizing antibodies (NAbs) blocked infection at multiple steps ...We evaluated the mechanism by which neutralizing human monoclonal antibodies inhibit chikungunya virus (CHIKV) infection. Potently neutralizing antibodies (NAbs) blocked infection at multiple steps of the virus life cycle, including entry and release. Cryo-electron microscopy structures of Fab fragments of two human NAbs and chikungunya virus-like particles showed a binding footprint that spanned independent domains on neighboring E2 subunits within one viral spike, suggesting a mechanism for inhibiting low-pH-dependent membrane fusion. Detailed epitope mapping identified amino acid E2-W64 as a critical interaction residue. An escape mutation (E2-W64G) at this residue rendered CHIKV attenuated in mice. Consistent with these data, CHIKV-E2-W64G failed to emerge in vivo under the selection pressure of one of the NAbs, IM-CKV063. As our study suggests that antibodies engaging the residue E2-W64 can potently inhibit CHIKV at multiple stages of infection, antibody-based therapies or immunogens that target this region might have protective value. |
リンク | Cell Rep / PubMed:26686638 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 11.2 - 15.3 Å |
構造データ | EMDB-6457: EMDB-6466: EMDB-6467: |
由来 |
|