中国病毒学2023，Issue(1) ：23-33.

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

Weijie Chen Yukun Li Xiuling Yu Zhenwei Wang Wenbiao Wang Menglan Rao Yongkui Li Zhen Luo Qiwei Zhang Jinbiao Liu Jianguo Wu
中国病毒学2023，Issue(1) ：23-33.
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Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral infection

Weijie Chen 1Yukun Li 2Xiuling Yu 3Zhenwei Wang 3Wenbiao Wang 4Menglan Rao 3Yongkui Li 1Zhen Luo 1Qiwei Zhang 1Jinbiao Liu 1Jianguo Wu1
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作者信息

  • 1. Guangdong Provincial Key Laboratory of Virology,Institute of Medical Microbiology,Jinan University,Guangzhou,510632,China;Foshan Institute of Medical Microbiology,Foshan,528315,China
  • 2. Halison International Peace Hospital,Hebei Medical University,Hengshui,053000,China
  • 3. Guangdong Provincial Key Laboratory of Virology,Institute of Medical Microbiology,Jinan University,Guangzhou,510632,China
  • 4. Medical Research Center,Guangdong Provincial People'ss Hospital,Guangdong Academy of Medical Sciences,Guangzhou,510080,China
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Abstract

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-β and 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.

Key words

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)

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基金项目

National Natural Science Foundation of China(81730061)

National Natural Science Foundation of China(81802008)

Guangdong Basic and Applied Basic Research Foundation(2021A1515011272)

出版年

2023
中国病毒学
中国科学院武汉病毒研究所，中国微生物学会

中国病毒学

CSTPCDCSCD北大核心
影响因子：0.393
ISSN：1674-0769
参考文献量55
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