KIF5B-mediated internalization of FMDV promotes virus infection  

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作  者:Wei Zhang Fan Yang Yang Yang Weijun Cao Wenhua Shao Jiali Wang Mengyao Huang Zhitong Chen Xiaoyi Zhao Weiwei Li Zixiang Zhu Haixue Zheng 

机构地区:[1]State Key Laboratory for Animal Disease Control and Prevention,College of Veterinary Medicine,Lanzhou University,Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Lanzhou 730000,China [2]Gansu Province Research Center for Basic Disciplines of Pathogen Biology,Lanzhou 730046,China

出  处:《Virologica Sinica》2024年第3期378-389,共12页中国病毒学(英文版)

基  金:supported by the National Natural Sciences Foundation of China(No.32102639 and 32072831);the National Key Research and Development Program of China(No.2021YFD1800300);the Gansu Science Foundation for Distinguished Young Scholars(No.21JR7RA026);the Earmarked Fund for CARS-35,the Strategic Priority Research Program of the National Center of Technology Innovation for Pigs(No.NCTIP-XD/C03);the Science and Technology Major Project of Gansu Province(No.22ZD6NA001);the Natural Science Foundation of Gansu Province(No.22JR5RA034 and 23JRRA549);the open competition program of top ten critical priorities of Agricultural Science and Technology Innovation for the 14th Five-Year Plan of Guangdong Province(No.2023SDZG02);the Fundamental Research Funds for the Central Universities(No.lzujbky-2022-ey20).

摘  要:Foot-and-mouth disease(FMD)is a highly contagious and economically important disease,which is caused by the FMD virus(FMDV).Although the cell receptor for FMDV has been identified,the specific mechanism of FMDV internalization after infection remains unknown.In this study,we found that kinesin family member 5B(KIF5B)plays a vital role during FMDV internalization.Moreover,we confirmed the interaction between KIF5B and FMDV structural protein VP1 by co-immunoprecipitation(Co-IP)and co-localization in FMDV-infected cells.In particular,the stalk[amino acids(aa)413–678]domain of KIF5B was indispensable for KIF5B-VP1 interaction.Moreover,overexpression of KIF5B dramatically enhanced FMDV replication;consistently,knockdown or knockout of KIF5B suppressed FMDV replication.Furthermore,we also demonstrated that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating.KIF5B also promotes the transmission of viral particles to early and late endosomes during the early stages of infection.In conclusion,our results demonstrate that KIF5B promotes the internalization of FMDV via regulating clathrin uncoating and intracellular transport.This study may provide a new therapeutic target for developing FMDV antiviral drugs.

关 键 词:FMDV VP1 protein KIF5B ENDOSOME CLATHRIN 

分 类 号:R373[医药卫生—病原生物学]

 

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