{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T21:17:10Z","timestamp":1780694230337,"version":"3.54.1"},"reference-count":50,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,8,5]],"date-time":"2022-08-05T00:00:00Z","timestamp":1659657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81620108021"],"award-info":[{"award-number":["81620108021"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>During the long coevolution of human cytomegalovirus (HCMV) and humans, the host has formed a defense system of multiple layers to eradicate the invader, and the virus has developed various strategies to evade host surveillance programs. The intrinsic immunity primarily orchestrated by promyelocytic leukemia (PML) nuclear bodies (PML\u2010NBs) represents the first line of defense against HCMV infection. Here, we demonstrate that microrchidia family CW\u2010type zinc finger 3 (MORC3), a PML\u2010NBs component, is a restriction factor targeting HCMV infection. We show that depletion of MORC3 through knockdown by RNA interference or knockout by CRISPR\u2010Cas9 augmented immediate\u2010early protein 1\u00a0(IE1) gene expression and subsequent viral replication, and overexpressing MORC3 inhibited HCMV replication by suppressing IE1 gene expression. To relief the restriction, HCMV induces transient reduction of MORC3 protein level via the ubiquitin\u2010proteasome pathway during the immediate\u2010early to early stage. However, MORC3 transcription is upregulated, and the protein level recovers in the late stages. Further analyses with temporal\u2010controlled MORC3 expression and the major immediate\u2010early promoter (MIEP)\u2010based reporters show that MORC3 suppresses MIEP activity and consequent IE1 expression with the assistance of PML. Taken together, our data reveal that HCMV enforces temporary loss of MORC3 to evade its repression against the initiation of immediate\u2010early gene expression.<\/jats:p>","DOI":"10.1002\/jmv.28025","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T01:28:25Z","timestamp":1658798905000},"page":"5492-5506","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["MORC3 restricts human cytomegalovirus infection by suppressing the major immediate\u2010early promoter activity"],"prefix":"10.1002","volume":"94","author":[{"given":"Xue\u2010Hui","family":"Ma","sequence":"first","affiliation":[{"name":"Department of Gastroenterology Guangzhou Women and Children's Medical Center Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Xuan","family":"Yao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Virology, Wuhan Institute of 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