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Far beyond passive genomic elements, ERVs actively shape host evolution through complex mechanisms involving genetic innovation, immune modulation, and species adaptation. This review provides a comprehensive synthesis of ERV biology, highlighting recent advances in their classification, amplification mechanisms, and epigenetic silencing. Particular emphasis is placed on the cross-talk between ERVs and exogenous retroviruses (XRVs), demonstrating how receptor competition, recombination, and immune evasion contribute to virus-host co-evolution. We explore ERVs as molecular markers for phylogenetic reconstruction, with case studies such as Koala retrovirus (KoRV) and HERV-K illustrating regional transmission dynamics and co-opted immune functions. Additionally, we discuss the functional domestication of ERVs into regulatory elements, non-coding RNAs, and envelope-derived fusion proteins that influence gene expression, antiviral defense, and placental development.<\/jats:p>","DOI":"10.3390\/genes16080964","type":"journal-article","created":{"date-parts":[[2025,8,15]],"date-time":"2025-08-15T10:33:42Z","timestamp":1755254022000},"page":"964","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Endogenous Retroviruses in Host-Virus Coevolution: From Genomic Domestication to Functional Innovation"],"prefix":"10.3390","volume":"16","author":[{"given":"Ruqi","family":"Jiang","sequence":"first","affiliation":[{"name":"Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-1267-8422","authenticated-orcid":false,"given":"Jingjun","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yue","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-9062-1852","authenticated-orcid":false,"given":"Guanjin","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Fan","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7136-7729","authenticated-orcid":false,"given":"Lixin","family":"Xiang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3671-2504","authenticated-orcid":false,"given":"Ye","family":"Chen","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzhong","family":"Shao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Cell and Molecular Intelligent Design and Development of Zhejiang Province, College of Life Sciences, Zhejiang University, Hangzhou 310058, China"},{"name":"Laboratory for Marine Biology and Biotechnology, Qingdao Marine Science and Technology Center, Qingdao 266071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Weiss, R. 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