PMID- 36211339
OWN - NLM
STAT- MEDLINE
DCOM- 20221011
LR  - 20221014
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 13
DP  - 2022
TI  - Herpes simplex virus type 2 inhibits TNF-alpha-induced NF-kappaB activation through viral 
      protein ICP22-mediated interaction with p65.
PG  - 983502
LID - 10.3389/fimmu.2022.983502 [doi]
LID - 983502
AB  - Herpes simplex virus type 2 (HSV-2) is a prevalent human pathogen and the main 
      cause of genital herpes. After initial infection, HSV-2 can establish lifelong 
      latency within dorsal root ganglia by evading the innate immunity of the host. 
      NF-kappaB has a crucial role in regulating cell proliferation, inflammation, 
      apoptosis, and immune responses. It is known that inhibition of NF-kappaB activation 
      by a virus could facilitate it to establish infection in the host. In the current 
      study, we found that HSV-2 inhibited TNF-alpha-induced activation of NF-kappaB-responsive 
      promoter in a dose-dependent manner, while UV-inactivated HSV-2 did not have such 
      capability. We further identified the immediate early protein ICP22 of HSV-2 as a 
      vital viral element in inhibiting the activation of NF-kappaB-responsive promoter. 
      The role of ICP22 was confirmed in human cervical cell line HeLa and primary 
      cervical fibroblasts in the context of HSV-2 infection, showing that ICP22 
      deficient HSV-2 largely lost the capability in suppressing NF-kappaB activation. 
      HSV-2 ICP22 was further shown to suppress the activity of TNF receptor-associated 
      factor 2 (TRAF2)-, IkappaB kinase alpha (IKK alpha)-, IKK beta-, IKK gamma-, or p65-induced 
      activation of NF-kappaB-responsive promoter. Mechanistically, HSV-2 ICP22 inhibited 
      the phosphorylation and nuclear translocation of p65 by directly interacting with 
      p65, resulting in the blockade of NF-kappaB activation. Furthermore, ICP22 from 
      several alpha-herpesviruses could also inhibit NF-kappaB activation, suggesting the 
      significance of ICP22 in herpesvirus immune evasion. Findings in this study 
      highlight the importance of ICP22 in inhibiting NF-kappaB activation, revealing a 
      novel mechanism by which HSV-2 evades the host antiviral responses.
CI  - Copyright (c) 2022 Hu, Fu, Li, Zhang, Li, Hu and Zhang.
FAU - Hu, Huimin
AU  - Hu H
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Center for 
      Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
AD  - Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
FAU - Fu, Ming
AU  - Fu M
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Center for 
      Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
AD  - Department of Gastroenterology, Guangzhou Women and Children's Medical Center, 
      Guangzhou Medical University, Guangzhou, China.
FAU - Li, Chuntian
AU  - Li C
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Center for 
      Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
AD  - Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
FAU - Zhang, Binman
AU  - Zhang B
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Center for 
      Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
AD  - Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
FAU - Li, Yuncheng
AU  - Li Y
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Center for 
      Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
AD  - Savaid Medical School, University of Chinese Academy of Sciences, Beijing, China.
FAU - Hu, Qinxue
AU  - Hu Q
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Center for 
      Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
AD  - Institute for Infection and Immunity, St George's, University of London, London, 
      United Kingdom.
FAU - Zhang, Mudan
AU  - Zhang M
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Center for 
      Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
LA  - eng
PT  - Journal Article
DEP - 20220923
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
RN  - 0 (Antiviral Agents)
RN  - 0 (ICP22 protein, human herpesvirus 1)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (TNF Receptor-Associated Factor 2)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 0 (Viral Proteins)
RN  - EC 2.7.11.10 (I-kappa B Kinase)
SB  - IM
MH  - Antiviral Agents
MH  - *Herpesvirus 1, Human/metabolism
MH  - Herpesvirus 2, Human/metabolism
MH  - Humans
MH  - I-kappa B Kinase/metabolism
MH  - *Immediate-Early Proteins/genetics/metabolism
MH  - NF-kappa B/metabolism
MH  - TNF Receptor-Associated Factor 2/metabolism
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Viral Proteins/metabolism
PMC - PMC9538160
OTO - NOTNLM
OT  - HSV-2
OT  - ICP22
OT  - NF-kappaB
OT  - immune evasion
OT  - p65
COIS- The authors declare that the research was conducted in the absence of any 
      commercial or financial relationships that could be construed as a potential 
      conflict of interest.
EDAT- 2022/10/11 06:00
MHDA- 2022/10/12 06:00
PMCR- 2022/01/01
CRDT- 2022/10/10 03:52
PHST- 2022/07/01 00:00 [received]
PHST- 2022/09/06 00:00 [accepted]
PHST- 2022/10/10 03:52 [entrez]
PHST- 2022/10/11 06:00 [pubmed]
PHST- 2022/10/12 06:00 [medline]
PHST- 2022/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2022.983502 [doi]
PST - epublish
SO  - Front Immunol. 2022 Sep 23;13:983502. doi: 10.3389/fimmu.2022.983502. eCollection 
      2022.