{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:45:29Z","timestamp":1792518329097,"version":"4.5.0"},"reference-count":138,"publisher":"Public Library of Science (PLoS)","issue":"10","license":[{"start":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:00:00Z","timestamp":1792454400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100013699","name":"Bundesministerium f\u00fcr Bildung, Wissenschaft und Forschung","doi-asserted-by":"publisher","award":["01KI2105"],"award-info":[{"award-number":["01KI2105"]}],"id":[{"id":"10.13039\/501100013699","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI164559"],"award-info":[{"award-number":["UM1AI164559"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI164559"],"award-info":[{"award-number":["UM1AI164559"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["UM1AI164559"],"award-info":[{"award-number":["UM1AI164559"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","award":["TI07.005"],"award-info":[{"award-number":["TI07.005"]}],"id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Research Foundation","award":["SFB1328\/ID: 335447717"],"award-info":[{"award-number":["SFB1328\/ID: 335447717"]}],"id":[{"id":"https:\/\/ror.org\/018mejw64","id-type":"ROR","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    People living with HIV (PLWH) on antiretroviral therapy (ART) accumulate primarily defective proviral sequences in genomes of often clonally expanded CD4\u2009+\u2009HIV-1 target cells. The majority of viral-derived DNA is transcriptionally active and preferentially found at distinct genomic loci suggesting a selective process driven by integration site-specific crosstalk between viral and host sequences. Focusing on one of the most prominent selected integration loci, the BTB Domain and CNC Homolog 2 (\n                    <jats:italic>BACH2<\/jats:italic>\n                    ) gene, we here show mechanistic insights how CD4\u2009+\u2009T cells are functionally reprogrammed via exaptation of provirus-derived regulatory sequences during long-term ART. Using a cellular model of\n                    <jats:italic>BACH2<\/jats:italic>\n                    -integrated proviruses, we find that proviral transcription drives aberrant BACH2 protein levels that escape autoregulatory feedback and impose BACH2-dependent transcriptomic changes. By mimicking these changes in primary CD4\u2009+\u2009T lymphocytes, we observe that BACH2 drives reprogramming of cells toward a proliferative, precursor memory-like type. These reprogrammed CD4\u2009+\u2009T cells possess traits of immune evasion and cellular survival that are signatures of persistent HIV reservoir cells in PLWH. Inhibition of provirus transcriptional activity can mitigate exaptation, suggesting a strategy to offset HIV-driven differentiation and expansion of CD4\u2009+\u2009T cells. Finally, our data suggest that provirus exaptation at a second prominently selected proviral integration gene, the Signal Transducer And Activator of Transcription 5B (STAT5B) gene, drives a contrary, effector-like T cell fate, suggesting a multifaceted impact of exaptation on immune homeostasis. Overall, our data suggest that transcriptionally active proviruses, even if structurally defective, modulate target cells through insertional activation of integration genes, a process which we postulate to contribute to the complex immune modulation and dysregulation experienced by ART-suppressed PLWH.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1014618","type":"journal-article","created":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T17:20:57Z","timestamp":1792516857000},"page":"e1014618","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Selective persistence of HIV-1-infected T cell clones can occur through immune reprogramming driven by defective, transcriptionally active proviruses"],"prefix":"10.1371","volume":"22","author":[{"given":"Martin V.","family":"Hamann","sequence":"first","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Unit Genomics of Retroviral Infections"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Brauckmann","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Unit Genomics of Retroviral Infections"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Unit Genomics of Retroviral Infections"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Spohn","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg\u2013Eppendorf","place":["Hamburg, Germany"],"department":["Bioinformatics Core"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Stoeck","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Unit Genomics of Retroviral Infections"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina M.","family":"Leddy","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Unit Genomics of Retroviral Infections"]},{"name":"Cornell University","place":["Ithaca, New York, United States of America"],"department":["Department of Molecular Biology and Genetics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Frouard","sequence":"additional","affiliation":[{"name":"University of California San Francisco (UCSF)","place":["San Francisco, California, United States of America"],"department":["Gladstone Institutes"]},{"name":"University of California San Francisco (UCSF)","place":["San Francisco, California, United States of America"],"department":["Department of Urology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maisha","family":"Adiba","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Unit Genomics of Retroviral Infections"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riekje","family":"Winzer","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"],"department":["Institute of Immunology"]},{"name":"University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"],"department":["Hamburg Center for Translational Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6110-5824","authenticated-orcid":true,"given":"Fabian","family":"Hausmann","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Department Integrative Virology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanamjeet","family":"Virdi","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Department Virus Genomics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Grundhoff","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Department Virus Genomics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cedric","family":"Feschotte","sequence":"additional","affiliation":[{"name":"Cornell University","place":["Ithaca, New York, United States of America"],"department":["Department of Molecular Biology and Genetics"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7665-0040","authenticated-orcid":true,"given":"Daniel","family":"Sauter","sequence":"additional","affiliation":[{"name":"University Hospital T\u00fcbingen","place":["T\u00fcbingen, Germany"],"department":["Institute for Medical Virology and Epidemiology of Viral Diseases"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frauke","family":"Muecksch","sequence":"additional","affiliation":[{"name":"Virology, Heidelberg University","place":["Heidelberg, Germany"],"department":["Department of Infectious Diseases"]},{"name":"German Center for Infection Research (DZIF)","place":["Braunschweig, Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia R.","family":"Roan","sequence":"additional","affiliation":[{"name":"University of California San Francisco (UCSF)","place":["San Francisco, California, United States of America"],"department":["Gladstone Institutes"]},{"name":"University of California San Francisco (UCSF)","place":["San Francisco, California, United States of America"],"department":["Department of Urology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Tolosa","sequence":"additional","affiliation":[{"name":"University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"],"department":["Institute of Immunology"]},{"name":"University Medical Center Hamburg-Eppendorf","place":["Hamburg, Germany"],"department":["Hamburg Center for Translational Immunology"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5274-3108","authenticated-orcid":true,"given":"Ulrike C.","family":"Lange","sequence":"additional","affiliation":[{"name":"Leibniz Institute of Virology","place":["Hamburg, Germany"],"department":["Research Unit Genomics of Retroviral Infections"]},{"name":"German Center for Infection Research (DZIF)","place":["Braunschweig, Germany"]},{"name":"I","place":["Hamburg, Germany"],"department":["nstitute for Infection Research and Vaccine Development"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,10,20]]},"reference":[{"issue":"8","key":"ppat.1014618.ref001","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1016\/j.it.2022.06.002","article-title":"An ordeal that does not heal: understanding barriers to a cure for HIV-1 infection","volume":"43","author":"M Lichterfeld","year":"2022","journal-title":"Trends Immunol"},{"issue":"4","key":"ppat.1014618.ref002","doi-asserted-by":"crossref","first-page":"519","DOI":"10.1016\/j.chom.2020.03.014","article-title":"The Biology of the HIV-1 Latent Reservoir and Implications for Cure Strategies","volume":"27","author":"LB Cohn","year":"2020","journal-title":"Cell Host 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