Lai, Jenn-HaungJenn-HaungLaiWu, De-WeiDe-WeiWuWu, Chien-HsiangChien-HsiangWuHung, Li-FengLi-FengHungHuang, Chuan-YuehChuan-YuehHuangKa, Shuk-ManShuk-ManKaChen, AnnAnnChenZEE-FEN CHANGHo, Ling-JunLing-JunHo2021-07-022021-07-022021-06-2525890042https://scholars.lib.ntu.edu.tw/handle/123456789/568266Mitochondria 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.enImmunology; Molecular biology; Virology[SDGs]SDG3journal article10.1016/j.isci.2021.102498341420252-s2.0-85106351950https://api.elsevier.com/content/abstract/scopus_id/85106351950