Structural basis for antibody-mediated neutralization of lymphocytic choriomeningitis virus.
Structural basis for antibody-mediated neutralization of lymphocytic choriomeningitis virus.
复制标题
抗体介导的淋巴细胞脉络膜脑膜炎病毒中和的结构基础。
DOI：
10.1016/j.chembiol.2023.03.005
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发表时间：
2023
影响因子：
8.6
通讯作者：
Saphire,EricaOllmann
中科院分区：
文献类型：
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作者：
Moon-Walker,Alex;Zhang,Zeli;Zyla,DawidS;Buck,TierraK;Li,Haoyang;DiazAvalos,Ruben;Schendel,SharonL;Hastie,KathrynM;Crotty,Shane;Saphire,EricaOllmann
乳头状病毒淋巴细胞性脉络丛脑膜炎病毒（LCMV）是一种全球分布的人畜共患病原体，对免疫功能低下的患者可能是致命的，如果在怀孕期间感染，可能导致严重的出生缺陷。三聚体表面糖蛋白的结构对进入、疫苗设计和抗体中和至关重要，目前仍不清楚。在这里，我们展示了LCMV表面糖蛋白（GP）单独和与合理设计的单克隆中和抗体18.5C-M28 （M28）复合的三聚体预融合组装中的冷冻电镜（cro - em）结构。此外，我们发现被动给药M28，无论是作为预防还是治疗，都可以保护小鼠免受LCMV克隆13 （LCMVcl13）的攻击。我们的研究不仅阐明了LCMV GP的整体结构组织及其被M28抑制的机制，而且还提出了一种有希望的治疗候选药物，用于预防有感染危险的个体严重或致命的疾病，这种病毒在全球范围内构成威胁。
The mammarenavirus lymphocytic choriomeningitis virus (LCMV) is a globally distributed zoonotic pathogen that can be lethal in immunocompromised patients and can cause severe birth defects if acquired during pregnancy. The structure of the trimeric surface glycoprotein, essential for entry, vaccine design, and antibody neutralization, remains unknown. Here, we present the cryoelectron microscopy (cryo-EM) structure of the LCMV surface glycoprotein (GP) in its trimeric pre-fusion assembly both alone and in complex with a rationally engineered monoclonal neutralizing antibody termed 18.5C-M28 (M28). Additionally, we show that passive administration of M28, either as a prophylactic or therapeutic, protects mice from LCMV clone 13 (LCMVcl13) challenge. Our study illuminates not only the overall structural organization of LCMV GP and the mechanism for its inhibition by M28 but also presents a promising therapeutic candidate to prevent severe or fatal disease in individuals who are at risk of infection by a virus that poses a threat worldwide.