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Identification of residues in Lassa virus glycoprotein 1 involved in receptor switch

Virologica Sinica 2024年第4期39卷 600-608页

作者： Jiao Guo Yi Wan Yang Liu Xiaoying Jia Siqi Dong Gengfu Xiao Wei Wang State Key Laboratory of Virology Wuhan Institute of VirologyCenter for Biosafety Mega-ScienceChinese Academy of SciencesWuhan 430071China University of the Chinese Academy of Sciences Beijing 100049China The Xi'an Key Laboratory of Pathogenic Microorganism and Tumor Immunity School of Basic MedicineXi'an Medical UniversityXi'an 710021China

Lassa virus(LASV)is an enveloped,negative-sense RNA virus that causes Lassa hemorrhagic *** entry of LASV requires the viral glycoprotein 1(GP1)to undergo a receptor switch from its primary receptor alpha-dystroglycan(α-DG)to its endosomal receptor lysosome-associated membrane protein 1(LAMP1).A conserved histidine triad in LASV GP1 has been reported to be responsible for receptor *** test the hypothesis that other non-conserved residues also contribute to receptor switch,we constructed a series of mutant LASV GP1 proteins and tested them for binding to *** residues,L84,K88,L107,and H170,were identified as critical for receptor *** any of the four residues with the corresponding lymphocytic choriomeningitis virus(LCMV)residue(L84 N,K88E,L10F,and H170S)reduced the binding affinity of LASV GP1 for ***,all mutations caused decreases in glycoprotein precursor(GPC)-mediated membrane fusion at both pH 4.5 and *** infectivity of pseudotyped viruses bearing either GPCL84N or GPCK88E decreased sharply in multiple cell types,while L107F and H170S had only mild effects on *** biolayer light interferometry assay,we found that all four mutants had decreased binding affinity to LAMP1,in the order of binding affinity being L84 N>L107F>K88E>*** four amino acid loci identified for the first time in this study have important reference significance for the in-depth investigation of the mechanism of receptor switching and immune escape of LASV occurrence and the development of reserve anti-LASV infection drugs.

关键词： Lassa virus(LASV) lysosome-associated membrane protein 1 (LAMP1) Glycoprotein Receptor switch membrane fusion

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