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

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

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
Available online: 12 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

Electronic Supplementary Material

10.1016j.virs.2023.04.003-ESM1.docx
10.1016j.virs.2023.04.003-ESM2.mp4
10.1016j.virs.2023.04.003-ESM3.mp4

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