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While the roles of latent or integrated viral genomes in cancer have been documented, emerging evidence highlights the contribution of defective viruses\u2014those carrying intragenic deletions or loss-of-function mutations\u2014in promoting viral oncogenesis. These altered genomes often lack genes essential for lytic replication or immune recognition, which enhances their persistence and immune evasion. In virus-associated diseases, specific patterns of gene retention and deletion suggest that host-driven selective pressures drive the emergence of these altered genomes. This review examines the generation, prevalence, and functional impact of these viruses, reframing them as active participants in disease development and progression. Recognizing their role offers new insights into viral tumor evolution and creates opportunities for applications in viral diagnostics and targeted intervention strategies.<\/jats:p>","DOI":"10.1093\/femsre\/fuaf048","type":"journal-article","created":{"date-parts":[[2025,9,26]],"date-time":"2025-09-26T15:47:10Z","timestamp":1758901630000},"source":"Crossref","is-referenced-by-count":2,"title":["Defective but tumorigenic: the evolutionary and functional roles of mutated oncoviruses"],"prefix":"10.1093","volume":"49","author":[{"given":"Yoshitaka","family":"Sato","sequence":"first","affiliation":[{"name":"Nagoya University Graduate School of Medicine Department of Virology, , Nagoya 466-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Okuno","sequence":"additional","affiliation":[{"name":"Nagoya City University Graduate School of Medical Sciences Department of Virology, , Nagoya 467-8601 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7228-0839","authenticated-orcid":false,"given":"Takayuki","family":"Murata","sequence":"additional","affiliation":[{"name":"Fujita Health University School of Medicine Department of Virology, , Toyoake 470-1192 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8063-5660","authenticated-orcid":false,"given":"Hiroshi","family":"Kimura","sequence":"additional","affiliation":[{"name":"Nagoya University Graduate School of Medicine Department of Virology, , Nagoya 466-8550 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,9,26]]},"reference":[{"key":"2025101007365201800_bib1","doi-asserted-by":"publisher","first-page":"1720","DOI":"10.1038\/s41375-022-01620-2","article-title":"The 5th edition of the World Health Organization 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