删除第一个糖基化位点可促进拉萨病毒糖蛋白介导的膜融合。

Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion.

机构信息

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430207, China; University of the Chinese Academy of Sciences, Beijing, 100049, China.

State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430207, China.

出版信息

Virol Sin. 2023 Jun;38(3):380-386. doi: 10.1016/j.virs.2023.04.003. Epub 2023 Apr 12.

DOI:10.1016/j.virs.2023.04.003

PMID:37059226

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10311258/

Abstract

The Lassa virus (LASV) is endemic in West Africa and causes severe hemorrhagic Lassa fever in humans. The glycoprotein complex (GPC) of LASV is highly glycosylation-modified, with 11 N-glycosylation sites. All 11 N-linked glycan chains play critical roles in GPC cleavage, folding, receptor binding, membrane fusion, and immune evasion. In this study, we focused on the first glycosylation site because its deletion mutant (N79Q) results in an unexpected enhanced membrane fusion, whereas it exerts little effect on GPC expression, cleavage, and receptor binding. Meanwhile, the pseudotype virus bearing GPC was more sensitive to the neutralizing antibody 37.7H and was attenuated in virulence. Exploring the biological functions of the key glycosylation site on LASV GPC will help elucidate the mechanism of LASV infection and provide strategies for the development of attenuated vaccines against LASV infection.

摘要

拉沙病毒（LASV）在西非流行，可导致人类发生严重的出血性拉沙热。LASV 的糖蛋白复合物（GPC）高度糖基化修饰，具有 11 个 N-糖基化位点。所有 11 个 N 连接聚糖链在 GPC 裂解、折叠、受体结合、膜融合和免疫逃逸中都发挥着关键作用。在这项研究中，我们专注于第一个糖基化位点，因为其缺失突变体（N79Q）会导致意想不到的增强的膜融合，而对 GPC 的表达、裂解和受体结合几乎没有影响。同时，携带 GPC 的假型病毒对中和抗体 37.7H 更加敏感，且毒力减弱。探索 LASV GPC 上关键糖基化位点的生物学功能将有助于阐明 LASV 感染的机制，并为开发针对 LASV 感染的减毒疫苗提供策略。