2. Academic Validation
  3. Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways

Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways

  • iScience. 2021 May 3;24(6):102498. doi: 10.1016/j.isci.2021.102498.
Jenn-Haung Lai 1,  De-Wei Wu 1,  Chien-Hsiang Wu 1,  Li-Feng Hung 2,  Chuan-Yueh Huang 2,  Shuk-Man Ka 3,  Ann Chen 4,  Zee-Fen Chang 5,  Ling-Jun Ho 2
Affiliations

Affiliations

  • 1 Department of Rheumatology, Allergy and Immunology, Chang Gung Memorial Hospital, Lin-Kou, Tao-Yuan, Taiwan, R.O.C.
  • 2 Institute of Cellular and System Medicine, National Health Research Institute, Zhunan, Taiwan, R.O.C.
  • 3 Graduate Institute of Aerospace and Undersea Medicine, Department of Medicine, National Defense Medical Center, Taipei, Taiwan, ROC.
  • 4 Department of Pathology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
  • 5 Institute of Molecular Medicine, College of Medicine, National Taiwan University, Taipei 10002, Taiwan.
PMID: 34142025 DOI: 10.1016/j.isci.2021.102498
Abstract

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-α) 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.

Keywords

Immunology; Molecular biology; Virology.

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