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

Siqi Dong; Wenting Mao; Yang Liu; Xiaoying Jia; Yueli Zhang; Minmin Zhou; Yuxia Hou; Gengfu Xiao; Wei Wang

doi:10.1016/j.virs.2023.04.003

June 2023

. doi: 10.1016/j.virs.2023.04.003

Citation: Siqi Dong, Wenting Mao, Yang Liu, Xiaoying Jia, Yueli Zhang, Minmin Zhou, Yuxia Hou, Gengfu Xiao, Wei Wang. Deletion of the first glycosylation site promotes Lassa virus glycoprotein-mediated membrane fusion .VIROLOGICA SINICA, 2023, 38(3) : 380-386. http://dx.doi.org/10.1016/j.virs.2023.04.003

拉沙病毒糖蛋白第一个糖基化位点的缺失促进病毒膜融合

董思琦 ^a,b ,
毛文婷 ^a,b ,
刘洋 ^a ,
贾潇瑛 ^a,b ,
张月丽 ^a,c ,
周旻旻 ^a,b ,
侯宇霞 ^a,b ,
肖庚富 ^a,b ,
王薇 ^a,b,,

a. 中国科学院武汉病毒研究所, 武汉, 430207, 中国;
b. 中国科学院大学, 北京, 100049, 中国;
c. 南开大学药学院, 天津, 300071, 中国

通讯作者： 王薇, wangwei@wh.iov.cn
收稿日期： 2023-01-11
录用日期： 2023-04-10

摘要

拉沙病毒（Lassa virus，LASV）属于沙粒病毒科（Arenaviridae）哺乳类沙粒病毒属（Mammarenavirus），主要在西非流行，会引起人类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，有11个N-糖基化位点。糖链均匀包裹在病毒颗粒的表面，会遮蔽GPC上的抗原和中和表位，并参与调控病毒蛋白折叠、受体识别和免疫逃避。在这项研究中，我们着重研究了第一个糖基化位点，因为它的缺失突变体（N79Q）会出乎意料地导致膜融合增强，而它对GPC的表达、裂解和受体结合的影响很小。同时，外包GPC_N79Q的假病毒对中和抗体37.7H更敏感，而且其毒力减弱。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，并为开发抗LASV感染的减毒疫苗提供策略。
- 拉沙病毒
- , 包膜糖蛋白
- , 糖基化位点
- , 膜融合

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

Siqi Dong ^a,b ,
Wenting Mao ^a,b ,
Yang Liu ^a ,
Xiaoying Jia ^a,b ,
Yueli Zhang ^a,c ,
Minmin Zhou ^a,b ,
Yuxia Hou ^a,b ,
Gengfu Xiao ^a,b ,
Wei Wang ^a,b,,

a. State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, 430207, China;
b. University of the Chinese Academy of Sciences, Beijing, 100049, China;
c. College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, 300071, China

Corresponding author: Wei Wang, wangwei@wh.iov.cn
Received Date: 11 January 2023
Accepted Date: 10 April 2023

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_N79Q 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.
- Lassa virus (LASV)
- , Glycoprotein complex (GPC)
- , Glycosylation site
- , Membrane fusion

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