ジャーナル: Proc Natl Acad Sci U S A / 年: 2020 タイトル: Structural basis of Chikungunya virus inhibition by monoclonal antibodies. 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 / 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.
全体 : Localized reconstruction of subregions around the icosahedral 5-f...
全体
名称: Localized reconstruction of subregions around the icosahedral 5-fold vertex of CHIKV:CHK-263 Fab complex
要素
複合体: Localized reconstruction of subregions around the icosahedral 5-fold vertex of CHIKV:CHK-263 Fab complex
細胞器官・細胞要素: Chikungunya virus
タンパク質・ペプチド: E1 glycoprotein
タンパク質・ペプチド: E2 glycoprotein
タンパク質・ペプチド: Capsid protein
細胞器官・細胞要素: Fab region of CHK-263
タンパク質・ペプチド: Fab heavy chain
タンパク質・ペプチド: Fab light chain
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超分子 #1: Localized reconstruction of subregions around the icosahedral 5-f...
超分子
名称: Localized reconstruction of subregions around the icosahedral 5-fold vertex of CHIKV:CHK-263 Fab complex タイプ: complex / ID: 1 / 親要素: 0 / 含まれる分子: all