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

第一糖基化位点的缺失促进拉沙病毒糖蛋白介导的膜融合。

• 影响指数: 6.947
• 发表时间: Jun 2023 12
• 来源期刊: Virol Sin
• DOI: 10.1016/j.virs.2023.04.003
• PMID: 37059226
• 文章类型: Journal Article
• 中科院分区: Q4
• 方向: 医学
• 作者列表: Dong S,Mao W,Liu Y,Jia X,Zhang Y,Zhou M,Hou Y,Xiao G,Wang W

关键词: Glycoprotein complex (GPC); Glycosylation site; Lassa virus (LASV); Membrane fusion

Mesh: Humans; Lassa virus / genetics; Glycosylation; Membrane Fusion; Glycoproteins / genetics; Lassa Fever / prevention & control

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 GPCN79Q 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

拉沙病毒在西非流行，并在人类中引起严重的出血性拉沙热。LASV的糖蛋白复合物（GPC）是高度糖基化修饰的，具有11个N-糖基化位点。所有11个N-连接的聚糖链在GPC裂解中起关键作用，折叠,受体结合，膜融合,和免疫逃避。在这项研究中,我们专注于第一个糖基化位点，因为它的缺失突变体（N79Q）导致意想不到的增强膜融合，而它对GPC表达几乎没有影响，乳沟,和受体结合。同时,携带GPCN79Q的假型病毒对中和抗体37.7H更敏感，毒力减弱。探索LASVGPC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。