PMID- 34142025
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210619
IS  - 2589-0042 (Electronic)
IS  - 2589-0042 (Linking)
VI  - 24
IP  - 6
DP  - 2021 Jun 25
TI  - Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities through 
      IFN-dependent and IFN-independent pathways.
PG  - 102498
LID - 10.1016/j.isci.2021.102498 [doi]
LID - 102498
AB  - Mitochondria regulate the immune response after dengue virus (DENV) infection. 
      Microarray analysis of genes identified the upregulation of mitochondrial 
      cytidine/uridine monophosphate kinase 2 (CMPK2) by DENV infection. We used small 
      interfering RNA-mediated knockdown (KD) and CRISPR-Cas9 knockout (KO) approaches, 
      to investigate the role of CMPK2 in mouse and human cells. The results showed 
      that CMPK2 was critical in DENV-induced antiviral cytokine release and 
      mitochondrial oxidative stress and mitochondrial DNA release to the cytosol. The 
      DENV-induced activation of Toll-like receptor (TLR)-9, inflammasome pathway, and 
      cell migration was suppressed by CMPK2 depletion; however, viral production 
      increased under CMPK2 deficiency. Examining mouse bone marrow-derived dendritic 
      cells from interferon-alpha (IFN-alpha) receptor-KO mice and signal transducer and 
      activator of transcription 1 (STAT1)-KO mice, we confirmed that CMPK2-mediated 
      antiviral activity occurred in IFN-dependent and IFN-independent manners. In sum, 
      CMPK2 is a critical factor in DENV-induced immune responses to determine innate 
      immunity.
CI  - (c) 2021.
FAU - Lai, Jenn-Haung
AU  - Lai JH
AD  - Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, 
      Lin-Kou, Tao-Yuan, Taiwan, R.O.C.
FAU - Wu, De-Wei
AU  - Wu DW
AD  - Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, 
      Lin-Kou, Tao-Yuan, Taiwan, R.O.C.
FAU - Wu, Chien-Hsiang
AU  - Wu CH
AD  - Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, 
      Lin-Kou, Tao-Yuan, Taiwan, R.O.C.
FAU - Hung, Li-Feng
AU  - Hung LF
AD  - Institute of Cellular and System Medicine, National Health Research Institute, 
      Zhunan, Taiwan, R.O.C.
FAU - Huang, Chuan-Yueh
AU  - Huang CY
AD  - Institute of Cellular and System Medicine, National Health Research Institute, 
      Zhunan, Taiwan, R.O.C.
FAU - Ka, Shuk-Man
AU  - Ka SM
AD  - Graduate Institute of Aerospace and Undersea Medicine, Department of Medicine, 
      National Defense Medical Center, Taipei, Taiwan, ROC.
FAU - Chen, Ann
AU  - Chen A
AD  - Department of Pathology, Tri-Service General Hospital, National Defense Medical 
      Center, Taipei, Taiwan.
FAU - Chang, Zee-Fen
AU  - Chang ZF
AD  - Institute of Molecular Medicine, College of Medicine, National Taiwan University, 
      Taipei 10002, Taiwan.
FAU - Ho, Ling-Jun
AU  - Ho LJ
AD  - Institute of Cellular and System Medicine, National Health Research Institute, 
      Zhunan, Taiwan, R.O.C.
LA  - eng
PT  - Journal Article
DEP - 20210503
PL  - United States
TA  - iScience
JT  - iScience
JID - 101724038
PMC - PMC8188380
OTO - NOTNLM
OT  - Immunology
OT  - Molecular biology
OT  - Virology
COIS- The authors confirm that there are no conflicts of interest.
EDAT- 2021/06/19 06:00
MHDA- 2021/06/19 06:01
PMCR- 2021/05/03
CRDT- 2021/06/18 06:52
PHST- 2020/12/07 00:00 [received]
PHST- 2021/03/31 00:00 [revised]
PHST- 2021/04/28 00:00 [accepted]
PHST- 2021/06/18 06:52 [entrez]
PHST- 2021/06/19 06:00 [pubmed]
PHST- 2021/06/19 06:01 [medline]
PHST- 2021/05/03 00:00 [pmc-release]
AID - S2589-0042(21)00466-1 [pii]
AID - 102498 [pii]
AID - 10.1016/j.isci.2021.102498 [doi]
PST - epublish
SO  - iScience. 2021 May 3;24(6):102498. doi: 10.1016/j.isci.2021.102498. eCollection 
      2021 Jun 25.