+検索条件
-Structure paper
タイトル | Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane. |
---|---|
ジャーナル・号・ページ | Cell Host Microbe, Vol. 24, Issue 3, Page 417-428.e5, Year 2018 |
掲載日 | 2018年9月12日 |
著者 | Jing Jin / Jesús G Galaz-Montoya / Michael B Sherman / Stella Y Sun / Cynthia S Goldsmith / Eileen T O'Toole / Larry Ackerman / Lars-Anders Carlson / Scott C Weaver / Wah Chiu / Graham Simmons / |
PubMed 要旨 | Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune ...Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. In addition, antibodies can engage Fc receptors (FcRs) on immune cells to activate antiviral responses. We describe a mechanism by which NAbs inhibit chikungunya virus (CHIKV), the most common alphavirus infecting humans, by preventing virus budding from infected human cells and activating IgG-specific Fcγ receptors. NAbs bind to CHIKV glycoproteins on the infected cell surface and induce glycoprotein coalescence, preventing budding of nascent virions and leaving structurally heterogeneous nucleocapsids arrested in the cytosol. Furthermore, NAbs induce clustering of CHIKV replication spherules at sites of budding blockage. Functionally, these densely packed glycoprotein-NAb complexes on infected cells activate Fcγ receptors, inducing a strong, antibody-dependent, cell-mediated cytotoxicity response from immune effector cells. Our findings describe a triply functional antiviral pathway for NAbs that might be broadly applicable across virus-host systems, suggesting avenues for therapeutic innovation through antibody design. |
リンク | Cell Host Microbe / PubMed:30146390 / PubMed Central |
手法 | EM (サブトモグラム平均) |
解像度 | 34.0 - 36.0 Å |
構造データ | EMDB-7513: EMDB-7515: |