https://scholars.lib.ntu.edu.tw/handle/123456789/568266
標題: | Mitochondrial CMPK2 mediates immunomodulatory and antiviral activities through IFN-dependent and IFN-independent pathways | 作者: | Lai, Jenn-Haung Wu, De-Wei Wu, Chien-Hsiang Hung, Li-Feng Huang, Chuan-Yueh Ka, Shuk-Man Chen, Ann ZEE-FEN CHANG Ho, Ling-Jun |
關鍵字: | Immunology; Molecular biology; Virology | 公開日期: | 25-六月-2021 | 卷: | 24 | 期: | 6 | 來源出版物: | iScience | 摘要: | 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. |
URI: | https://scholars.lib.ntu.edu.tw/handle/123456789/568266 | ISSN: | 25890042 | DOI: | 10.1016/j.isci.2021.102498 |
顯示於: | 分子醫學研究所 |
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