PMID- 37597377
OWN - NLM
STAT- MEDLINE
DCOM- 20230920
LR  - 20230920
IS  - 1873-2542 (Electronic)
IS  - 0378-1135 (Linking)
VI  - 284
DP  - 2023 Sep
TI  - Japanese encephalitis virus NS4B inhibits interferon beta production by targeting 
      TLR3 and TRIF.
PG  - 109849
LID - S0378-1135(23)00201-8 [pii]
LID - 10.1016/j.vetmic.2023.109849 [doi]
AB  - Japanese encephalitis virus (JEV) is a flavivirus transmitted by mosquitoes, 
      causing epidemics of encephalitis in humans and reproductive disorders in pigs. 
      This virus is predominantly distributed in Asian countries and causes tens of 
      thousands of infections in humans annually. Interferon (IFN) is an essential 
      component of host defense against viral infection. Multiple studies have 
      indicated that multifunctional nonstructural proteins of flaviviruses suppress 
      the host IFN response via various strategies to facilitate viral replication. The 
      flaviviruses encoded nonstructural protein 4B (NS4B) is a multifunctional 
      hydrophobic nonstructural protein widely involved in viral replication, 
      pathogenesis and host immune evasion. In this study, we demonstrated that NS4B of 
      JEV suppressed the induction of IFN-beta production, mainly through targeting the 
      TLR3 and TRIF (a TIR domain-containing linker that induces IFN-beta) proteins in the 
      TLR3 pathway. In a dual-luciferase reporter assay, JEV NS4B significantly 
      inhibited the activation of IFN-beta promoter induced by TLR3 and simultaneously 
      treated with poly (I:C). Moreover, NS4B also inhibited the activation of IFN-beta 
      promoter triggered by interferon regulatory factor 3 (IRF3)/5D or its upstream 
      molecules in TLR3 signaling pathway. Furthermore, NS4B inhibited the 
      phosphorylation of IRF3 under the stimulation of TLR3 and TRIF molecules. 
      Mechanistically, JEV NS4B interacts with TLR3 and TRIF and confirmed by 
      co-localization and co-immunoprecipitation assay, thereby inhibiting the 
      activation of downstream sensors in the TLR3-mediated pathway. Overall, our 
      results provide a novel mechanism by which JEV NS4B interferes with the host's 
      antiviral response through targeting TLR3 receptor signaling pathway.
CI  - Copyright (c) 2023 Elsevier B.V. All rights reserved.
FAU - Zeng, Quan
AU  - Zeng Q
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, 
      Henan, China.
FAU - Liu, Jiaqi
AU  - Liu J
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, 
      Henan, China.
FAU - Li, Zhaoyang
AU  - Li Z
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, 
      Henan, China.
FAU - Zhang, Yucan
AU  - Zhang Y
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, 
      Henan, China.
FAU - Zu, Shaopo
AU  - Zu S
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, 
      Henan, China; Key Laboratory for Animal-derived Food Safety of Henan Province, 
      Zhengzhou 450002, China; Ministry of Education Key Laboratory for Animal 
      Pathogens and Biosafety, Zhengzhou 450002, China.
FAU - Ding, Xueyan
AU  - Ding X
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, 
      Henan, China; Key Laboratory for Animal-derived Food Safety of Henan Province, 
      Zhengzhou 450002, China; Ministry of Education Key Laboratory for Animal 
      Pathogens and Biosafety, Zhengzhou 450002, China.
FAU - Zhang, Honglei
AU  - Zhang H
AD  - College of Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, 
      Henan, China; Key Laboratory for Animal-derived Food Safety of Henan Province, 
      Zhengzhou 450002, China; Ministry of Education Key Laboratory for Animal 
      Pathogens and Biosafety, Zhengzhou 450002, China. Electronic address: 
      hongleizhang2012@163.com.
LA  - eng
PT  - Journal Article
DEP - 20230815
PL  - Netherlands
TA  - Vet Microbiol
JT  - Veterinary microbiology
JID - 7705469
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 77238-31-4 (Interferon-beta)
RN  - 9008-11-1 (Interferons)
RN  - 0 (TLR3 protein, human)
RN  - 0 (Toll-Like Receptor 3)
SB  - IM
MH  - Animals
MH  - Adaptor Proteins, Vesicular Transport/genetics
MH  - *Encephalitis Virus, Japanese/genetics
MH  - Interferon-beta/genetics
MH  - Interferons
MH  - Swine
MH  - Toll-Like Receptor 3/genetics
OTO - NOTNLM
OT  - IFN-beta
OT  - Japanese encephalitis virus
OT  - NS4B protein
OT  - TLR3
OT  - TRIF
COIS- Declaration of Competing Interest We declare that we have no conflict of 
      interest. Moreover, we have no financial and personal relationships with other 
      people or organizations that can inappropriately influence our work.
EDAT- 2023/08/20 00:41
MHDA- 2023/09/04 06:42
CRDT- 2023/08/19 18:05
PHST- 2023/06/07 00:00 [received]
PHST- 2023/08/10 00:00 [revised]
PHST- 2023/08/11 00:00 [accepted]
PHST- 2023/09/04 06:42 [medline]
PHST- 2023/08/20 00:41 [pubmed]
PHST- 2023/08/19 18:05 [entrez]
AID - S0378-1135(23)00201-8 [pii]
AID - 10.1016/j.vetmic.2023.109849 [doi]
PST - ppublish
SO  - Vet Microbiol. 2023 Sep;284:109849. doi: 10.1016/j.vetmic.2023.109849. Epub 2023 
      Aug 15.