中国病毒学2023,Vol.38Issue(3) :380-386.DOI:10.1016/j.virs.2023.04.003

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
中国病毒学2023,Vol.38Issue(3) :380-386.DOI:10.1016/j.virs.2023.04.003

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

Siqi Dong 1Wenting Mao 1Yang Liu 2Xiaoying Jia 1Yueli Zhang 3Minmin Zhou 1Yuxia Hou 1Gengfu Xiao 1Wei Wang1
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作者信息

  • 1. 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
  • 2. State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430207,China
  • 3. State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan,430207,China;College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology,Nankai University,Tianjin,300071,China
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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.

Key words

Lassa virus(LASV)/Glycoprotein complex(GPC)/Glycosylation site/Membrane fusion

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基金项目

National Key Research and Development Program(2022YFC2303300)

National Key Research and Development Program(2018YFA0507204)

Strategic Priority Research Program of the Chinese Academy of Sciences(XDB0490000)

National Natural Science Foundation of China(82172273)

National Natural Science Foundation of China(31670165)

出版年

2023
中国病毒学
中国科学院武汉病毒研究所,中国微生物学会

中国病毒学

CSTPCDCSCD
影响因子:0.393
ISSN:1674-0769
参考文献量29
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