Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection  

作　　者：Weijie Chen Yukun Li Xiuling Yu Zhenwei Wang Wenbiao Wang Menglan Rao Yongkui Li Zhen Luo Qiwei Zhang Jinbiao Liu Jianguo Wu 

机构地区：[1]Guangdong Provincial Key Laboratory of Virology,Institute of Medical Microbiology,Jinan University,Guangzhou,510632,China [2]Foshan Institute of Medical Microbiology,Foshan,528315,China [3]Halison International Peace Hospital,Hebei Medical University,Hengshui,053000,China [4]Medical Research Center,Guangdong Provincial People's Hospital,Guangdong Academy of Medical Sciences,Guangzhou,510080,China

出　　处：《Virologica Sinica》2023年第1期23-33,共11页中国病毒学（英文版）

基　　金：supported by the National Natural Science Foundation of China(81730061,81802008);the Guangdong Basic and Applied Basic Research Foundation(2021A1515011272).

摘　　要：Zika virus(ZIKV)evolves non-structural proteins to evade immune response and ensure efficient replication in the host cells.Cholesterol metabolic enzyme 7-dehydrocholesterol reductase(DHCR7)was recently reported to impact innate immune responses in ZIKV infection.However,the vital non-structural protein and mechanisms involved in DHCR7-mediated viral evasion are not well elucidated.In this study,we demonstrated that ZIKV infection facilitated DHCR7 expression.Notably,the upregulated DHCR7 in turn facilitated ZIKV infection and blocking DHCR7 suppressed ZIKV infection.Mechanically,ZIKV non-structural protein 4B(NS4B)interacted with DHCR7 to induce DHCR7 expression.Moreover,DHCR7 inhibited TANK-binding kinase 1(TBK1)and interferon regulatory factor 3(IRF3)phosphorylation,which resulted in the reduction of interferon-beta(IFN-β)and interferon-stimulated genes(ISGs)productions.Therefore,we propose that ZIKV NS4B binds to DHCR7 to repress TBK1 and IRF3 activation,which in turn inhibits IFN-βand ISGs,and thereby facilitating ZIKV evasion.This study broadens the insights on how viral non-structural proteins antagonize innate immunity to facilitate viral infection via cholesterol metabolic enzymes and intermediates.

关 键 词：7-Dehydrocholesterol reductase(DHCR7) Interferon regulatory factor 3(IRF3) Interferon-beta(IFN-β) Non-structural protein 4B(NS4B) TANK-Binding kinase 1(TBK1) Zika virus(ZIKV) 

分 类 号：R392[医药卫生—免疫学]