{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T20:44:28Z","timestamp":1783457068719,"version":"3.55.0"},"reference-count":76,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,28]],"date-time":"2025-06-28T00:00:00Z","timestamp":1751068800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"American Cancer Society","award":["IRG21-145-25"],"award-info":[{"award-number":["IRG21-145-25"]}]},{"name":"American Cancer Society","award":["R01 CA180758"],"award-info":[{"award-number":["R01 CA180758"]}]},{"name":"Department of Interdisciplinary Oncology, LSU-LCMC Cancer Center, Louisiana State University Health Science Center, New Orleans","award":["IRG21-145-25"],"award-info":[{"award-number":["IRG21-145-25"]}]},{"name":"Department of Interdisciplinary Oncology, LSU-LCMC Cancer Center, Louisiana State University Health Science Center, New Orleans","award":["R01 CA180758"],"award-info":[{"award-number":["R01 CA180758"]}]},{"name":"Public Health Service","award":["IRG21-145-25"],"award-info":[{"award-number":["IRG21-145-25"]}]},{"name":"Public Health Service","award":["R01 CA180758"],"award-info":[{"award-number":["R01 CA180758"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>IFI16 is a well-characterized nuclear innate immune DNA sensor that detects foreign dsDNA, including herpesviral genomes, to activate the inflammasome and interferon pathways. Beyond immune signaling, IFI16 also functions as an antiviral restriction factor, promoting the silencing of invading viral genes through transcriptional and epigenetic mechanisms. We recently demonstrated another role of IFI16, in which it interacts with and recruits the class I histone deacetylases, HDAC1 and 2, to the KSHV latency protein LANA, modulating its acetylation and function. In this study, we asked whether these IFI16-HDAC1\/2 interactions contribute to broader epigenetic regulation of the KSHV chromatin. Our findings reveal that IFI16 associates with and facilitates the recruitment of the NuRD and Sin3A co-repressor complexes\u2014both multiprotein, HDAC1\/2-containing chromatin regulators\u2014on KSHV episomes. Depletion of IFI16 led to reductions in NuRD and Sin3A occupancy on viral chromatin, accompanied by increased histone acetylation at lytic gene promoters. These results suggest that IFI16 plays a critical role in recruiting or stabilizing these HDAC-containing co-repressor complexes on the KSHV genome, thereby enforcing transcriptional silencing of lytic genes and maintaining latency in KSHV. Our study expands the known functions of IFI16 and identifies a novel epigenetic mechanism by which it modulates herpesviral chromatin states.<\/jats:p>","DOI":"10.3390\/v17070921","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"921","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["IFI16 Mediates Deacetylation of KSHV Chromatin via Interaction with NuRD and Sin3A Co-Repressor Complexes"],"prefix":"10.3390","volume":"17","author":[{"given":"Anandita","family":"Ghosh","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bala","family":"Chandran","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8486-0539","authenticated-orcid":false,"given":"Arunava","family":"Roy","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Morsani College of Medicine, University of South Florida, Tampa, FL 33620, USA"},{"name":"Department of Interdisciplinary Oncology, LSU-LCMC Cancer Center, Louisiana State University Health, New Orleans, LA 70112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1056\/NEJM199505043321802","article-title":"Kaposi\u2019s sarcoma-associated herpesvirus-like DNA sequences in AIDS-related body-cavity-based lymphomas","volume":"332","author":"Ethel","year":"1995","journal-title":"N. 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