Identification of RACK1 as a novel regulator of non-structural protein 4 of chikungunya virus  

作　　者：Yao Yan Fengyuan Zhang Meng Zou Hongyu Chen Jingwen Xu Shuaiyao Lu Hongqi Liu 

机构地区：[1]Institute of Medical Biology,Chinese Academy of Medical Sciences and Peking Union Medical College,Kunming 650118,China [2]National Human Diseases Animal Model Resource Center,NHC Key Laboratory of Human Disease Comparative Medicine,National Center of Technology Innovation for Animal Model,State Key Laboratory of Respiratory Health and Multimorbidity,and Key Laboratory of Pathogen Infection Prevention and Control,Ministry of Education,Institute of Laboratory Animal Sciences,Chinese Academy of Medical Sciences and Peking Union Medical College,Beijing 100021 China

出　　处：《Acta Biochimica et Biophysica Sinica》2024年第10期1425-1436,共12页生物化学与生物物理学报（英文版）

基　　金：supported by the grants from the Yunnan Key R&D Project(No.202103AQ100001);the Foundation of the CAMS Initiative for Innovative Medicine(Nos.2021-I2M-1-036 and 2021-I2M-1-043);the Fundamental Research Funds for the Central Universities(No.3332022072).

摘　　要：Chikungunya virus(CHIKV)is a neglected arthropod-borne and anthropogenic alphavirus.Over the past two decades,the CHIKV distribution has undergone significant changes worldwide,from the original tropics and subtropics regions to temperate regions,which has attracted global attention.However,the interactions between CHIKV and its host remain insufficiently understood,which dampens the need for the development of an anti-CHIKV strategy.In this study,on the basis of the optimal overexpression of non-structural protein 4(nsP4),we explore host interactions of CHIKV nsP4 using mass spectrometry-based protein-protein interaction approaches.The results reveal that some cellular proteins that interact with nsP4 are enriched in the ubiquitin-proteasome pathway.Specifically,the scaffold protein receptor for activated C kinase 1(RACK1)is identified as a novel host interactor and regulator of CHIKV nsP4.The inhibition of the interaction between RACK1 and nsP4 by harringtonolide results in the reduction of nsP4,which is caused by the promotion of degradation but not the inhibition of nsP4 translation.Furthermore,the decrease in nsP4 triggered by the RACK1 inhibitor can be reversed by the proteasome inhibitor MG132,suggesting that RACK1 can protect nsP4 from degradation through the ubiquitin-proteasome pathway.This study reveals a novel mechanism by which the host factor RACK1 regulates CHIKV nsP4,which could be a potential target for developing drugs against CHIKV.

关 键 词：Chikungunya virus non-structural protein 4 RACK1 ubiquitin-proteasome pathway 

分 类 号：R373[医药卫生—病原生物学]