The mechanistic basis of protection by non-neutralizing anti-alphavirus antibodies.
The mechanistic basis of protection by non-neutralizing anti-alphavirus antibodies.
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DOI：
10.1016/j.celrep.2021.108962
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发表时间：
2021-04-06
期刊：
影响因子：
8.8
通讯作者：
Diamond MS
中科院分区：
文献类型：
--
作者：
Earnest JT;Holmes AC;Basore K;Mack M;Fremont DH;Diamond MS
尽管针对甲病毒 E2 蛋白内表位的中和单克隆抗体 (mAb) 可以预防感染，但非中和单克隆抗体的功能意义却知之甚少。在这里，我们评估了 13 种非中和性单克隆抗体针对 Mayaro 病毒 (MAYV)（一种新兴的致关节炎甲病毒）的活性。这些 mAb 与 MAYV 病毒粒子和受感染细胞的表面结合，但无法中和细胞培养物中的感染。绘图研究确定了六个 mAb 结合基团，它们定位于 E2 糖蛋白 A 结构域内或邻近的离散表位。值得注意的是，非中和性单克隆抗体的被动转移可以保护小鼠免受 MAYV 感染和疾病，其功效需要 Fc 效应子功能。单核细胞在体内介导非中和性单克隆抗体的保护，因为表达 Fcγ 受体的骨髓细胞促进 MAYV 的结合、摄取和清除，而无需抗体依赖性增强感染。针对甲病毒的体液保护可能反映了非中和抗体通过 Fc 依赖性机制加速病毒清除的贡献。欧尼斯特等人。描述针对 Mayaro 病毒（一种新兴的致关节炎甲病毒）的保护性抗体反应。他们发现，小鼠体内抗体介导的保护不需要病毒中和，而是依赖于与骨髓细胞相关的 Fc 效应器功能。
Although neutralizing monoclonal antibodies (mAbs) against epitopes within the alphavirus E2 protein can protect against infection, the functional significance of non-neutralizing mAbs is poorly understood. Here, we evaluate the activity of 13 non-neutralizing mAbs against Mayaro virus (MAYV), an emerging arthritogenic alphavirus. These mAbs bind to the MAYV virion and surface of infected cells but fail to neutralize infection in cell culture. Mapping studies identify six mAb binding groups that localize to discrete epitopes within or adjacent to the A domain of the E2 glycoprotein. Remarkably, passive transfer of non-neutralizing mAbs protects against MAYV infection and disease in mice, and their efficacy requires Fc effector functions. Monocytes mediate the protection of non-neutralizing mAbs in vivo, as Fcγ-receptor-expressing myeloid cells facilitate the binding, uptake, and clearance of MAYV without antibody-dependent enhancement of infection. Humoral protection against alphaviruses likely reflects contributions from non-neutralizing antibodies through Fc-dependent mechanisms that accelerate viral clearance. Earnest et al. characterize the protective antibody response against Mayaro virus, an emerging arthritogenic alphavirus. They find that antibody-mediated protection in mice does not require virus neutralization but can rely on Fc effector functions associated with myeloid cells.
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影响因子：
30.5
作者：
Dejnirattisai W;Supasa P;Wongwiwat W;Rouvinski A;Barba-Spaeth G;Duangchinda T;Sakuntabhai A;Cao-Lormeau VM;Malasit P;Rey FA;Mongkolsapaya J;Screaton GR
通讯作者：
Screaton GR
影响因子：
11.8
作者：
Halsey ES;Siles C;Guevara C;Vilcarromero S;Jhonston EJ;Ramal C;Aguilar PV;Ampuero JS
通讯作者：
Ampuero JS
DOI：
10.1084/jem.20151267
发表时间：
2015-08-24
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Bournazos S;DiLillo DJ;Ravetch JV
通讯作者：
Ravetch JV
影响因子：
11.8
作者：
Azevedo, Raimunda S. S.;Silva, Eliana V. P.;Vasconcelos, Pedro F. C.
通讯作者：
Vasconcelos, Pedro F. C.
影响因子：
3.8
作者：
Choi, Hyeree;Kudchodkar, Sagar B.;Muthumani, Kar
通讯作者：
Muthumani, Kar