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-Structure paper
タイトル | Structural basis of Chikungunya virus inhibition by monoclonal antibodies. |
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ジャーナル・号・ページ | Proc Natl Acad Sci U S A, Vol. 117, Issue 44, Page 27637-27645, Year 2020 |
掲載日 | 2020年11月3日 |
著者 | Qun Fei Zhou / Julie M Fox / James T Earnest / Thiam-Seng Ng / Arthur S Kim / Guntur Fibriansah / Victor A Kostyuchenko / Jian Shi / Bo Shu / Michael S Diamond / Shee-Mei Lok / |
PubMed 要旨 | Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute and chronic debilitating arthritis. Here, we describe the functional and structural basis as to how two anti-CHIKV ...Chikungunya virus (CHIKV) is an emerging viral pathogen that causes both acute and chronic debilitating arthritis. Here, we describe the functional and structural basis as to how two anti-CHIKV monoclonal antibodies, CHK-124 and CHK-263, potently inhibit CHIKV infection in vitro and in vivo. Our in vitro studies show that CHK-124 and CHK-263 block CHIKV at multiple stages of viral infection. CHK-124 aggregates virus particles and blocks attachment. Also, due to antibody-induced virus aggregation, fusion with endosomes and egress are inhibited. CHK-263 neutralizes CHIKV infection mainly by blocking virus attachment and fusion. To determine the structural basis of neutralization, we generated cryogenic electron microscopy reconstructions of Fab:CHIKV complexes at 4- to 5-Å resolution. CHK-124 binds to the E2 domain B and overlaps with the Mxra8 receptor-binding site. CHK-263 blocks fusion by binding an epitope that spans across E1 and E2 and locks the heterodimer together, likely preventing structural rearrangements required for fusion. These results provide structural insight as to how neutralizing antibody engagement of CHIKV inhibits different stages of the viral life cycle, which could inform vaccine and therapeutic design. |
リンク | Proc Natl Acad Sci U S A / PubMed:33087569 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 4.5 - 9.4 Å |
構造データ | EMDB-30476, PDB-7cvy: EMDB-30477, PDB-7cvz: EMDB-30478, PDB-7cw0: EMDB-30479, PDB-7cw2: EMDB-30480, PDB-7cw3: |
由来 |
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キーワード | IMMUNE SYSTEM/VIRUS / CHIKV / Fab / complex / VIRUS / IMMUNE SYSTEM-VIRUS complex / VIRUS/IMMUNE SYSTEM / VIRUS-IMMUNE SYSTEM complex / IgG / localized reconstruction |