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In this study, we analyzed the variability and integration sites of persisting viruses in nine organs from thirteen individuals who died suddenly from non-viral\u00a0causes. The viruses studied\u00a0included parvovirus B19, six herpesviruses, Merkel cell (MCPyV) and JC polyomaviruses, totaling 127 genomes. The viral sequences across organs were remarkably conserved within each individual, suggesting that persistence stems from single dominant strains. This indicates that intra-host viral evolution, thus far inferred primarily from immunocompromised patients, is likely overestimated in healthy subjects. Indeed, we detected increased viral subpopulations in two individuals with putative reactivations, suggesting that replication status influences diversity. Furthermore, we identified asymmetrical mutation\u00a0patterns\u00a0reflecting\u00a0selective pressures exerted by the host. Strikingly, our analysis revealed non-clonal viral integrations even in individuals without cancer. These included MCPyV integrations and truncations resembling clonally expanded variants in\u00a0Merkel cell carcinomas, as well as novel junctions between herpesvirus 6B and mitochondrial sequences, the significance of which remains to be evaluated. Our work systematically characterizes the genomic landscape of the tissue-resident virome, highlighting potential deviations occurring during disease.<\/jats:p>","DOI":"10.1093\/nar\/gkae871","type":"journal-article","created":{"date-parts":[[2024,10,22]],"date-time":"2024-10-22T12:46:44Z","timestamp":1729601204000},"page":"13073-13093","source":"Crossref","is-referenced-by-count":10,"title":["Intra-host genomic diversity and integration landscape of human tissue-resident DNA virome"],"prefix":"10.1093","volume":"52","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9504-5807","authenticated-orcid":false,"given":"Lari","family":"Py\u00f6ri\u00e4","sequence":"first","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital , Haartmaninkatu 3, P.O. Box 21, FI-00014,\u00a0 Helsinki ,","place":["Finland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1176-552X","authenticated-orcid":false,"given":"Diogo","family":"Pratas","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital , Haartmaninkatu 3, P.O. Box 21, FI-00014,\u00a0 Helsinki ,","place":["Finland"]},{"name":"IEETA, Institute of Electronics and Informatics Engineering of Aveiro, and LASI, Intelligent Systems Associate Laboratory, University of Aveiro, Campus Universit\u00e1rio de Santiago , 3810-193,\u00a0 Aveiro ,","place":["Portugal"]},{"name":"Department of Electronics, Telecommunications and Informatics, University of Aveiro, Campus Universit\u00e1rio de Santiago , 3810-193,\u00a0 Aveiro ,","place":["Portugal"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1205-2399","authenticated-orcid":false,"given":"Mari","family":"Toppinen","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, University of Helsinki , Haartmaninkatu 3, P.O. Box 21, FI-00014,\u00a0 Helsinki ,","place":["Finland"]}]},{"given":"Peter","family":"Simmonds","sequence":"additional","affiliation":[{"name":"Nuffield Department of Medicine, University of Oxford , Peter Medawar Building, South Parks Road, OX1 3SY,\u00a0Oxford,","place":["UK"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1779-7960","authenticated-orcid":false,"given":"Klaus","family":"Hedman","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital , Haartmaninkatu 3, P.O. Box 21, FI-00014,\u00a0 Helsinki ,","place":["Finland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4117-5248","authenticated-orcid":false,"given":"Antti","family":"Sajantila","sequence":"additional","affiliation":[{"name":"Department of Forensic Medicine, University of Helsinki , Haartmaninkatu 3, P.O. Box 21, FI-00014,\u00a0 Helsinki ,","place":["Finland"]},{"name":"Forensic Medicine Unit, Finnish Institute for Health and Welfare , Mannerheimintie 166 A, P.O. Box 30, FI-00271, Helsinki ,","place":["Finland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-4251","authenticated-orcid":false,"given":"Maria\u00a0F","family":"Perdomo","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital , Haartmaninkatu 3, P.O. Box 21, FI-00014,\u00a0 Helsinki ,","place":["Finland"]}]}],"member":"286","published-online":{"date-parts":[[2024,10,22]]},"reference":[{"key":"2024112721480477500_B1","doi-asserted-by":"crossref","first-page":"2470","DOI":"10.1128\/JCM.00330-16","article-title":"Comparison of next-generation sequencing technologies for comprehensive assessment of full-length hepatitis C viral genomes","volume":"54","author":"Thomson","year":"2016","journal-title":"J. Clin. 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