Structural basis of Semliki Forest virus entry using the very-low-density lipoprotein receptor  

作　　者：Ying Li Zhennan Zhao Sheng Liu Haichen Wang Junqing Sun Yan Chai Jingya Zhou Yinuo Wang Yi Shi Hao Song George Fu Gao 

机构地区：[1]Savaid Medical School,University of Chinese Academy of Sciences,Beijing,China [2]CAS Key Laboratory of Pathogen Microbiology and Immunology,Institute of Microbiology,Chinese Academy of Sciences,Beijing,China [3]Cryo-EM Center,Southern University of Science and Technology,Guangdong,China [4]School of Life Sciences,Hebei University,Hebei,China [5]Research Network of Immunity and Health(RNIH),Beijing Institutes of Life Science,Chinese Academy of Sciences,Beijing,China [6]College of Veterinary Medicine,Shanxi Agricultural University,Shanxi,China

出　　处：《hLife》2023年第2期124-136,共13页健康科学（英文）

基　　金：supported by the National Natural Science Foundation of China (82072290,82122040,and 32100129);supported by CAS Project for Young Scientists in Basic Research (YSBR-010);the Youth Innovation Promotion Association CAS (Y2021033).

摘　　要：Alphaviruses are a group of important viruses that cause significant diseases in humans.Among them,Semliki Forest vi-rus(SFV)not only causes symptoms such as joint pain but also infects neuron cells and induces encephalitis in rodents.Recently,the very-low-density lipoprotein receptor(VLDLR)was identified as the cellular receptor for SFV entry.In this study,we present the cryo-electron microscopy structure of SFV bound to human VLDLR.VLDLR targets E1-DIII region of SFV using its membrane-distal LDLR class A(LA)repeats.Structural and functional analyses emphasize the synergistic role of multiple VLDLR repeats in the SFV entry.Remarkably,VLDLR’s binding mode to SFV closely mirrors that of minor group human rhinoviruses but differs significantly from other alphaviruses’interactions with receptors in the canyon re-gion of the E protein.We also assessed SFV binding to VLDLR or apolipoprotein E receptor 2(ApoER2)proteins in horses and mosquitoes and revealed their use of multiple but different LA repeats for binding.Our findings illuminate SFV’s cross-species infectivity,offering insights into potential antiviral strategies against alphavirus infections.

关 键 词：ALPHAVIRUS Semliki Forest virus very-low-density lipoprotein receptor cryo-electron microscopystruc-ture RECEPTOR viral entry 

分 类 号：R37[医药卫生—病原生物学]