{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T23:08:39Z","timestamp":1788390519245,"version":"build-2803163510"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013087","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T00:00:00Z","timestamp":1752192000000}}],"reference-count":101,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T00:00:00Z","timestamp":1751932800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R35 CA 200421"],"award-info":[{"award-number":["R35 CA 200421"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["RO1 AI 184043"],"award-info":[{"award-number":["RO1 AI 184043"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Oncogenic retroviruses are known for their pathogenesis via insertional mutagenesis, in which the presence of a provirus and its transcriptional control elements alter the expression of a nearby or surrounding host gene. There are reports of proviral integration driving oncogenesis in people with HIV and the use of HIV-derived vectors for gene therapy has raised concern about oncogenic side effects. To study this issue, we used an in vitro primary human CD4\u2009+\u2009T cell infection model developed in our laboratory to identify HIV-1 integration sites that might influence cell proliferation or survival. Combining integration site analysis and bulk RNA sequencing, we found that an upregulated\n                    <jats:italic>STAT3<\/jats:italic>\n                    signature due to proviral insertional mutagenesis was associated with persistent HIV-infected CD4\u2009+\u2009T cells. HIV+ persistent cells also expressed a STAT3-related anti-apoptotic and cytotoxic phenotype that resembles that of HIV-associated T cell lymphomas. HIV insertional mutagenesis of\n                    <jats:italic>STAT3<\/jats:italic>\n                    and expression of its downstream targets provides a model of HIV-associated T cell lymphomas that can be used to further determine the oncogenic drivers of HIV-associated lymphomas, both AIDS- and gene therapy-associated, and, potentially, to evaluate therapeutics against these HIV-associated cancers.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013087","type":"journal-article","created":{"date-parts":[[2025,7,8]],"date-time":"2025-07-08T15:31:41Z","timestamp":1751988701000},"page":"e1013087","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":4,"title":["In vitro HIV DNA integration in STAT3 drives T cell persistence\u2014A model of HIV-associated T cell lymphoma"],"prefix":"10.1371","volume":"21","author":[{"given":"Michael","family":"Rist","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Machika","family":"Kaku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3856-762X","authenticated-orcid":true,"given":"John M.","family":"Coffin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,7,8]]},"reference":[{"issue":"2","key":"ppat.1013087.ref001","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1016\/j.ymthe.2019.12.009","article-title":"Retroviral Insertional Mutagenesis in Humans: Evidence for Four Genetic Mechanisms Promoting Expansion of Cell Clones","volume":"28","author":"FD Bushman","year":"2020","journal-title":"Mol 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