PMID- 36182074
OWN - NLM
STAT- MEDLINE
DCOM- 20230301
LR  - 20230314
IS  - 1995-820X (Electronic)
IS  - 1674-0769 (Print)
IS  - 1995-820X (Linking)
VI  - 38
IP  - 1
DP  - 2023 Feb
TI  - Zika virus non-structural protein 4B interacts with DHCR7 to facilitate viral 
      infection.
PG  - 23-33
LID - S1995-820X(22)00157-2 [pii]
LID - 10.1016/j.virs.2022.09.009 [doi]
AB  - 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-beta) 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-beta 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.
CI  - Copyright (c) 2022 The Authors. Publishing services by Elsevier B.V. All rights 
      reserved.
FAU - Chen, Weijie
AU  - Chen W
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China; Foshan Institute of 
      Medical Microbiology, Foshan, 528315, China.
FAU - Li, Yukun
AU  - Li Y
AD  - Halison International Peace Hospital, Hebei Medical University, Hengshui, 053000, 
      China.
FAU - Yu, Xiuling
AU  - Yu X
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China.
FAU - Wang, Zhenwei
AU  - Wang Z
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China.
FAU - Wang, Wenbiao
AU  - Wang W
AD  - Medical Research Center, Guangdong Provincial People's Hospital, Guangdong 
      Academy of Medical Sciences, Guangzhou, 510080, China.
FAU - Rao, Menglan
AU  - Rao M
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China.
FAU - Li, Yongkui
AU  - Li Y
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China; Foshan Institute of 
      Medical Microbiology, Foshan, 528315, China.
FAU - Luo, Zhen
AU  - Luo Z
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China; Foshan Institute of 
      Medical Microbiology, Foshan, 528315, China.
FAU - Zhang, Qiwei
AU  - Zhang Q
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China; Foshan Institute of 
      Medical Microbiology, Foshan, 528315, China.
FAU - Liu, Jinbiao
AU  - Liu J
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China; Foshan Institute of 
      Medical Microbiology, Foshan, 528315, China. Electronic address: 
      jinbiaoliu@jnu.edu.cn.
FAU - Wu, Jianguo
AU  - Wu J
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University, Guangzhou, 510632, China; Foshan Institute of 
      Medical Microbiology, Foshan, 528315, China. Electronic address: 
      jwu898@jnu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20220929
PL  - Netherlands
TA  - Virol Sin
JT  - Virologica Sinica
JID - 101514185
RN  - 0 (Viral Nonstructural Proteins)
RN  - 77238-31-4 (Interferon-beta)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Humans
MH  - *Zika Virus
MH  - *Zika Virus Infection
MH  - Signal Transduction
MH  - Viral Nonstructural Proteins/metabolism
MH  - Interferon-beta/genetics/metabolism
MH  - Immunity, Innate
MH  - Cholesterol
MH  - Virus Replication
PMC - PMC10006206
OTO - NOTNLM
OT  - 7-Dehydrocholesterol reductase (DHCR7)
OT  - Interferon regulatory factor 3 (IRF3)
OT  - Interferon-beta (IFN-beta)
OT  - Non-structural protein 4B (NS4B)
OT  - TANK-Binding kinase 1 (TBK1)
OT  - Zika virus (ZIKV)
EDAT- 2022/10/02 06:00
MHDA- 2023/03/03 06:00
PMCR- 2022/09/29
CRDT- 2022/10/01 19:38
PHST- 2022/05/08 00:00 [received]
PHST- 2022/09/26 00:00 [accepted]
PHST- 2022/10/02 06:00 [pubmed]
PHST- 2023/03/03 06:00 [medline]
PHST- 2022/10/01 19:38 [entrez]
PHST- 2022/09/29 00:00 [pmc-release]
AID - S1995-820X(22)00157-2 [pii]
AID - 10.1016/j.virs.2022.09.009 [doi]
PST - ppublish
SO  - Virol Sin. 2023 Feb;38(1):23-33. doi: 10.1016/j.virs.2022.09.009. Epub 2022 Sep 
      29.