PMID- 33517839
OWN - NLM
STAT- MEDLINE
DCOM- 20210930
LR  - 20210930
IS  - 2150-5608 (Electronic)
IS  - 2150-5594 (Print)
IS  - 2150-5594 (Linking)
VI  - 12
IP  - 1
DP  - 2021 Dec
TI  - Sox4 represses host innate immunity to facilitate pathogen infection by hijacking 
      the TLR signaling networks.
PG  - 704-722
LID - 10.1080/21505594.2021.1882775 [doi]
AB  - Toll-like receptors (TLRs) are essential for the protection of the host from 
      pathogen infections by initiating the integration of contextual cues to regulate 
      inflammation and immunity. However, without tightly controlled immune responses, 
      the host will be subjected to detrimental outcomes. Therefore, it is important to 
      balance the positive and negative regulations of TLRs to eliminate pathogen 
      infection, yet avert harmful immunological consequences. This study revealed a 
      distinct mechanism underlying the regulation of the TLR network. The expression 
      of sex-determining region Y-box 4 (Sox4) is induced by virus infection in viral 
      infected patients and cultured cells, which subsequently represses the TLR 
      signaling network to facilitate viral replication at multiple levels by a 
      distinct mechanism. Briefly, Sox4 inhibits the production of myeloid 
      differentiation primary response gene 88 (MyD88) and most of the TLRs by binding 
      to their promoters to attenuate gene transcription. In addition, Sox4 blocks the 
      activities of the TLR/MyD88/IRAK4/TAK1 and TLR/TRIF/TRAF3/TBK1 pathways by 
      repressing their key components. Moreover, Sox4 represses the activation of the 
      nuclear factor kappa-B (NF-kappaB) through interacting with IKKalpha/alpha, and attenuates 
      NF-kB and IFN regulatory factors 3/7 (IRF3/7) abundances by promoting protein 
      degradation. All these contributed to the down-regulation of interferons (IFNs) 
      and IFN-stimulated gene (ISG) expression, leading to facilitate the viral 
      replications. Therefore, we reveal a distinct mechanism by which viral pathogens 
      evade host innate immunity and discover a key regulator in host defense.
FAU - Shang, Jian
AU  - Shang J
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University , Guangzhou, China.
FAU - Zheng, Yuan
AU  - Zheng Y
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University , 
      Wuhan, China.
FAU - Mo, Jiayin
AU  - Mo J
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University , 
      Wuhan, China.
FAU - Wang, Wenbiao
AU  - Wang W
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University , Guangzhou, China.
FAU - Luo, Zhen
AU  - Luo Z
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University , Guangzhou, China.
FAU - Li, Yongkui
AU  - Li Y
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University , Guangzhou, China.
FAU - Chen, Xulin
AU  - Chen X
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University , Guangzhou, China.
FAU - Zhang, Qiwei
AU  - Zhang Q
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University , Guangzhou, China.
FAU - Wu, Kailang
AU  - Wu K
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University , 
      Wuhan, China.
FAU - Liu, Weiyong
AU  - Liu W
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University , Guangzhou, China.
FAU - Wu, Jianguo
AU  - Wu J
AUID- ORCID: 0000-0002-8326-2895
AD  - Guangdong Provincial Key Laboratory of Virology, Institute of Medical 
      Microbiology, Jinan University , Guangzhou, China.
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University , 
      Wuhan, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Virulence
JT  - Virulence
JID - 101531386
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (SOX4 protein, human)
RN  - 0 (SOXC Transcription Factors)
RN  - 0 (Toll-Like Receptors)
SB  - IM
MH  - Enterovirus A, Human/immunology/pathogenicity
MH  - Hep G2 Cells
MH  - Humans
MH  - Immunity, Innate/*genetics/immunology
MH  - Influenza A virus/immunology/pathogenicity
MH  - Leukocytes, Mononuclear/immunology/virology
MH  - Myeloid Differentiation Factor 88/antagonists & inhibitors/immunology
MH  - SOXC Transcription Factors/*genetics/*immunology
MH  - Signal Transduction/genetics/*immunology
MH  - Toll-Like Receptors/genetics/immunology/*metabolism
MH  - Virus Replication
MH  - Viruses/*immunology/pathogenicity
PMC - PMC7894441
OTO - NOTNLM
OT  - EV71
OT  - Enterovirus 71
OT  - HCV
OT  - IAV
OT  - IFN
OT  - IFN regulatory factors 3/7
OT  - IFN-stimulated gene
OT  - IRF3/7
OT  - ISG
OT  - MyD88
OT  - SEV
OT  - Sox4
OT  - TLRS
OT  - Toll-like receptors
OT  - VSV
OT  - hepatitis C virus
OT  - influenza A virus
OT  - interferon
OT  - myeloid differentiation primary response gene 88
OT  - sendai virus
OT  - sex-determining region Y-box 4
OT  - vesicular stomatitis virus
EDAT- 2021/02/02 06:00
MHDA- 2021/10/01 06:00
PMCR- 2021/02/16
CRDT- 2021/02/01 05:29
PHST- 2021/02/02 06:00 [pubmed]
PHST- 2021/10/01 06:00 [medline]
PHST- 2021/02/01 05:29 [entrez]
PHST- 2021/02/16 00:00 [pmc-release]
AID - 1882775 [pii]
AID - 10.1080/21505594.2021.1882775 [doi]
PST - ppublish
SO  - Virulence. 2021 Dec;12(1):704-722. doi: 10.1080/21505594.2021.1882775.