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In this study, HCMV infection promoted the increase of mitochondrial fusion and caused mitochondrial dysfunction in THP\u20101 cells, including excessive reactive oxygen species production and decreased mitochondrial membrane potential (\u0394\u03c8m). Meanwhile, the expression of mitochondrial DNA (mtDNA)\u2010binding protein TFAM (transcription factor A, mitochondrial) was decreased and mtDNA content in the cytoplasm was increased. Knockdown of TFAM caused an increase in mtDNA copy number in the cytoplasm and resulted in elevated NLRP3 expression, active caspase\u20101, and mature IL\u20101\u03b2. After a 3 h treatment with MCC950, an NLRP3 inhibitor, the increase of cleaved caspase\u20101 and mature IL\u20101\u03b2 were suppressed. Besides, overexpression of TFAM inhibited the expression of NLRP3, cleaved caspase\u20101, and mature IL\u20101\u03b2. In addition, knockdown of NLRP3 inhibited the IL\u20101\u03b2 process after HCMV infection. mtDNA\u2010deficient cells showed a limited ability to produce NLRP3 and process IL\u20101\u03b2 after HCMV infection. In conclusion, HCMV infection of THP\u20101 cells resulted in decreased mitochondrial TFAM protein expression and increased mtDNA release into the cytoplasm, which eventually led to the activation of NLRP3 inflammasome.<\/jats:p>","DOI":"10.1111\/1348-0421.13063","type":"journal-article","created":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T04:14:05Z","timestamp":1679112845000},"page":"303-313","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Human cytomegalovirus infection activates NLRP3 inflammasome by releasing mtDNA into the cytosol in human THP\u20101 cells"],"prefix":"10.1111","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5094-3766","authenticated-orcid":false,"given":"Xi","family":"Xu","sequence":"first","affiliation":[{"name":"The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University Wenzhou Zhejiang China"},{"name":"School of Laboratory Medicine 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