Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane.
Neutralizing Antibodies Inhibit Chikungunya Virus Budding at the Plasma Membrane.
复制标题
DOI：
10.1016/j.chom.2018.07.018
复制
发表时间：
2018-09-12
影响因子：
30.3
通讯作者：
Simmons G
中科院分区：
文献类型：
--
作者：
Jin J;Galaz-Montoya JG;Sherman MB;Sun SY;Goldsmith CS;O'Toole ET;Ackerman L;Carlson LA;Weaver SC;Chiu W;Simmons G
传统上认为，中和抗体（nab）通过阻止病毒粒子进入靶细胞来抑制病毒感染。此外，抗体可以结合免疫细胞上的Fc受体（FcRs）来激活抗病毒反应。我们描述了一种nab抑制基孔肯雅病毒（CHIKV）的机制，通过阻止病毒从受感染的人细胞出芽和激活igg特异性Fcγ受体。基孔肯雅病毒是感染人类的最常见的甲病毒。nab与感染细胞表面的CHIKV糖蛋白结合，诱导糖蛋白结合，阻止新生病毒粒子出芽，并在细胞质中留下结构不均匀的核衣壳。此外，nab诱导CHIKV复制球粒在出芽阻塞部位聚集。功能上，这些被感染细胞上密集堆积的糖蛋白- nab复合物激活Fcγ受体，诱导免疫效应细胞产生强烈的、依赖抗体的、细胞介导的细胞毒性反应。我们的研究结果描述了nab的三重功能抗病毒途径，可能广泛适用于病毒-宿主系统，为通过抗体设计进行治疗创新提供了途径。Jin等人证明，中和抗体（nab）通过诱导病毒糖蛋白在感染细胞上聚结来抑制基孔肯雅病毒出芽。交联糖蛋白的nab与免疫细胞上的Fc受体结合，激活抗病毒反应。考虑到nab的经典进入抑制功能，本工作描述了nab的三重功能抗病毒途径。
Neutralizing antibodies (NAbs) are traditionally thought to inhibit virus infection by preventing virion entry into target cells. Additionally, 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. Jin et al. demonstrate that neutralizing antibodies (NAbs) inhibit chikungunya virus budding by inducing viral glycoprotein coalescence on infected cells. NAbs that crosslink glycoproteins engage Fc receptors on immune cells to activate antiviral responses. Considering the classical entry-inhibition function of NAbs, this work describes a triply-functional antiviral pathway for NAbs.
登录
查看更多内容
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.4
作者：
Kallio, Katri;Hellstrom, Kirsi;Ahola, Tero
通讯作者：
Ahola, Tero
影响因子：
3.7
作者：
Masrinoul, Promsin;Puiprom, Orapim;Okabayashi, Tamaki
通讯作者：
Okabayashi, Tamaki
影响因子：
3
作者：
Kremer, JR;Mastronarde, DN;McIntosh, JR
通讯作者：
McIntosh, JR
影响因子：
2.2
作者：
Corboba, P;Grutadauria, S;Zapata, M
通讯作者：
Zapata, M