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-Structure paper
タイトル | Human mAbs Broadly Protect against Arthritogenic Alphaviruses by Recognizing Conserved Elements of the Mxra8 Receptor-Binding Site. |
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ジャーナル・号・ページ | Cell Host Microbe, Vol. 28, Issue 5, Page 699-711.e7, Year 2020 |
掲載日 | 2020年11月11日 |
著者 | Laura A Powell / Andrew Miller / Julie M Fox / Nurgun Kose / Thomas Klose / Arthur S Kim / Robin Bombardi / Rashika N Tennekoon / A Dharshan de Silva / Robert H Carnahan / Michael S Diamond / Michael G Rossmann / Richard J Kuhn / James E Crowe / |
PubMed 要旨 | Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease ...Mosquito inoculation of humans with arthritogenic alphaviruses results in a febrile syndrome characterized by debilitating musculoskeletal pain and arthritis. Despite an expanding global disease burden, no approved therapies or licensed vaccines exist. Here, we describe human monoclonal antibodies (mAbs) that bind to and neutralize multiple distantly related alphaviruses. These mAbs compete for an antigenic site and prevent attachment to the recently discovered Mxra8 alphavirus receptor. Three cryoelectron microscopy structures of Fab in complex with Ross River (RRV), Mayaro, or chikungunya viruses reveal a conserved footprint of the broadly neutralizing mAb RRV-12 in a region of the E2 glycoprotein B domain. This mAb neutralizes virus in vitro by preventing virus entry and spread and is protective in vivo in mouse models. Thus, the RRV-12 mAb and its defined epitope have potential as a therapeutic agent or target of vaccine design against multiple emerging arthritogenic alphavirus infections. |
リンク | Cell Host Microbe / PubMed:32783883 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.8 - 6.33 Å |
構造データ | EMDB-21473, PDB-6vyv: EMDB-21496, PDB-6w09: EMDB-21509, PDB-6w1c: EMDB-21532: Native Mayaro virus cryo EM map, resolution 4.8 Angstroms |
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キーワード | VIRAL PROTEIN/IMMUNE SYSTEM / virus / monoclonal antibody / complex / VIRAL PROTEIN-IMMUNE SYSTEM complex / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex |