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Multiple mechanisms have been employed for endogenous retroviral deactivation, rendering replication and retrotransposition defective, while some of them have been co-opted to serve host evolutionary advantages. A pleiad of mechanisms retains the delicate balance of HERV expression in modern humans. Thus, epigenetic modifications, such as DNA and histone methylation, acetylation, deamination, chromatin remodeling, and even post-transcriptional control are recruited. In this review, we aim to summarize the main HERV silencing pathways, revisit paradigms of human disease with a HERV component, and emphasize the human immunodeficiency virus (HIV) and HERV interactions during HIV infection.<\/jats:p>","DOI":"10.3390\/genes15020192","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T08:44:06Z","timestamp":1706690646000},"page":"192","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["HERVs: Expression Control Mechanisms and Interactions in Diseases and Human Immunodeficiency Virus Infection"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-7560-5605","authenticated-orcid":false,"given":"Federica","family":"Mantovani","sequence":"first","affiliation":[{"name":"Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konstantina","family":"Kitsou","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0141-4753","authenticated-orcid":false,"given":"Gkikas","family":"Magiorkinis","sequence":"additional","affiliation":[{"name":"Department of Hygiene, Epidemiology and Medical Statistics, Medical School, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,1,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"MDNA3-0009-2014","DOI":"10.1128\/microbiolspec.MDNA3-0009-2014","article-title":"Mammalian Endogenous Retroviruses","volume":"3","author":"Mager","year":"2015","journal-title":"Microbiol. 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