Characterizing the Lassa Virus Envelope Glycoprotein Membrane Proximal External Region for Its Role in Fusogenicity  

作　　者：Junyuan Cao Guangshun Zhang Minmin Zhou Yang Liu Gengfu Xiao Wei Wang 

机构地区：[1]State Key Laboratory of Virology,Wuhan Institute of Virology,Center for Biosafety Mega-Science,Chinese Academy of Sciences,Wuhan 430071,China [2]University of the Chinese Academy of Sciences,Beijing 100049,China [3]College of Life Sciences,Nankai University,Tianjin 300353,China

出　　处：《Virologica Sinica》2021年第2期273-280,共8页中国病毒学（英文版）

基　　金：the National Key Research and Development Program of China (2018YFA0507204);the National Natural Sciences Foundation of China (31670165);Wuhan National Biosafety Laboratory,Chinese Academy of Sciences Advanced Customer Cultivation Project (2019ACCP-MS03);the Open Research Fund Program of the State Key Laboratory of Virology of China (2018IOV001)。

摘　　要：The membrane-proximal external region(MPER)of Lassa virus(LASV)glycoprotein complex(GPC)is critical in modulating its functionality.Till now,the high-resolution structure of the intact GPC,including MPER is not available.In this study,we used alanine substitution to scan all 16 residues located in LASV MPER.Western blotting and quantification fusion assay showed that the residues located at the C terminus of the HR2(M414 and L415)and N terminus of the MPER(K417 and Y419)are critical for GPC-mediated membrane fusion function.Furthermore,cell surface biotinylation experiments revealed that M414 A,K417 A and Y419 A expressed similar levels as WT,whereas L415 A mutant led to a reduction of mature GPC on the cell surface.Moreover,substitution of these residues with the similar residue such as M414 L,L415 I,K417 R and Y419 F would partly compensate the loss of the fusion activity caused by the alanine mutant in these sites.Results from this study showed that several key residues in the MPER region are indispensable to promote the conformational changes that drive fusion events and shed light on the structure analysis of LASV GPC and anti-LASV therapeutics.

关 键 词：Lassa virus(LASV) ARENAVIRUS Glycoprotein complex(GPC) Membrane-proximal external region(MPER) Membrane fusion 

分 类 号：R373[医药卫生—病原生物学]