{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,5]],"date-time":"2026-04-05T02:58:04Z","timestamp":1775357884682,"version":"3.50.1"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,5,20]],"date-time":"2024-05-20T00:00:00Z","timestamp":1716163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008723","name":"Finnish Medical Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008723","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Life and Health Medical Foundation"},{"name":"Helsinki University Hospital Research and Education Fund"},{"DOI":"10.13039\/100010135","name":"Finska L\u00e4kares\u00e4llskapet","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010135","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004155","name":"Magnus Ehrnrooth Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004155","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004012","name":"Jane and Aatos Erkko Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004012","id-type":"DOI","asserted-by":"publisher"}]},{"name":"R\u012bga Stradi\u0146\u0161 University Research Grant","award":["6-ZD-22\/4\/2023"],"award-info":[{"award-number":["6-ZD-22\/4\/2023"]}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UIDB\/00127\/2020"],"award-info":[{"award-number":["UIDB\/00127\/2020"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>The implications of inherited chromosomally integrated human herpesvirus 6 (iciHHV-6) in solid organ transplantation remain uncertain. Although this trait has been linked to unfavorable clinical outcomes, an association between viral reactivation and complications has only been conclusively established in a few cases.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>We used hybrid capture sequencing for in-depth analysis of the viral sequences reconstructed from sequential liver biopsies. Moreover, we investigated viral replication through in situ hybridization (U38\u2013U94 genes), reverse transcriptase polymerase chain reaction (U89\/U90 genes), immunohistochemistry, and immunofluorescence. We also performed whole transcriptome sequencing to profile the host immune response.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>We report a case of reactivation of a recipient\u2019s iciHHV-6B and subsequent infection of the graft. Using a novel approach integrating the analysis of viral and mitochondrial DNAs, we located the iciHHV-6B intragraft. We demonstrated active replication via the emergence of viral minor variants, in addition to positive viral messenger RNAs and antigen stainings in tissue sections. Furthermore, we detected significant upregulation of antiviral immune responses, arguing against immunotolerance.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Our analysis underscores the potential pathological impact of iciHHV-6B, emphasizing the need for monitoring reactivation in transplant recipients. Most crucially, it highlights the critical role that the host's virome can play in shaping the outcome of transplantation.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/infdis\/jiae268","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T20:25:45Z","timestamp":1715977545000},"page":"e267-e276","source":"Crossref","is-referenced-by-count":6,"title":["Reactivation of a Transplant Recipient's Inherited Human Herpesvirus 6 and Implications to the Graft"],"prefix":"10.1093","volume":"231","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5982-413X","authenticated-orcid":false,"given":"Leo","family":"Hannolainen","sequence":"first","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital ,","place":["Finland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9504-5807","authenticated-orcid":false,"given":"Lari","family":"Py\u00f6ri\u00e4","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital ,","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 ,","place":["Finland"]},{"name":"Department of Electronics, Telecommunications and Informatics, Institute of Electronics and Informatics Engineering of Aveiro, and Intelligent Systems Associate Laboratory, University of Aveiro ,","place":["Portugal"]}]},{"given":"Jouko","family":"Lohi","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Helsinki and Helsinki University Hospital ,","place":["Finland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3589-9429","authenticated-orcid":false,"given":"Sandra","family":"Skuja","sequence":"additional","affiliation":[{"name":"Joint Laboratory of Electron Microscopy, Institute of Anatomy and Anthropology"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6519-7121","authenticated-orcid":false,"given":"Santa","family":"Rasa-Dzelzkaleja","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Virology, R\u012bga Stradi\u0146\u0161 University , Riga ,","place":["Latvia"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0971-1784","authenticated-orcid":false,"given":"Modra","family":"Murovska","sequence":"additional","affiliation":[{"name":"Institute of Microbiology and Virology, R\u012bga Stradi\u0146\u0161 University , Riga ,","place":["Latvia"]}]},{"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 ,","place":["Finland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1815-7327","authenticated-orcid":false,"given":"Timo","family":"Jahnukainen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology and Transplantation, Children's Hospital and Helsinki University Hospital ,","place":["Finland"]}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-4251","authenticated-orcid":false,"given":"Maria Fernanda","family":"Perdomo","sequence":"additional","affiliation":[{"name":"Department of Virology, University of Helsinki and Helsinki University Hospital ,","place":["Finland"]}]}],"member":"286","published-online":{"date-parts":[[2024,5,20]]},"reference":[{"key":"2025022016343956300_jiae268-B1","doi-asserted-by":"crossref","first-page":"5563","DOI":"10.1073\/pnas.0913586107","article-title":"The latent human herpesvirus-6A genome specifically integrates in telomeres of human chromosomes in vivo and in 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