{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T22:23:23Z","timestamp":1776205403481,"version":"3.50.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013745","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,12,18]],"date-time":"2025-12-18T00:00:00Z","timestamp":1766016000000}}],"reference-count":62,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T00:00:00Z","timestamp":1765497600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["U54 AI170792, P30 AI117943, R01AI176599,R01AI167778, R01AI150455,R01AI165236, R01AI150998,R21 AI174864, R56AI174877"],"award-info":[{"award-number":["U54 AI170792, P30 AI117943, R01AI176599,R01AI167778, R01AI150455,R01AI165236, R01AI150998,R21 AI174864, R56AI174877"]}]},{"name":"NIH","award":["1P01AI169600, 1R01MH125778"],"award-info":[{"award-number":["1P01AI169600, 1R01MH125778"]}]},{"DOI":"10.13039\/100000997","name":"Arnold and Mabel Beckman Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000997","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Human immunodeficiency virus (HIV) relies upon a broad array of host factors in order to replicate and evade the host antiviral response. Cleavage and polyadenylation specificity factor 6 (CPSF6) is one such host factor that is recruited by incoming HIV-1 cores to regulate trafficking, nuclear import, uncoating, and integration site selection. Despite these well-described roles, the impact of CPSF6 perturbation on HIV-1 infectivity varies considerably by cell type. Here, we report that\n                    <jats:italic>CPSF6<\/jats:italic>\n                    knock-out in primary CD4+\u2009T cells leads to increased permissivity to HIV-1 infection due to broad transcriptional reprogramming. Knock-out of\n                    <jats:italic>CPSF6<\/jats:italic>\n                    results in widespread differential gene expression, including downregulation of genes involved in the innate immune response and enhanced expression of the HIV-1 co-receptors. Accordingly, these cells are less responsive to interferon and express lower levels of antiretroviral restriction factors, including TRIM5\u03b1. These transcriptional changes are linked to global shortening of mRNA 3\u2019 untranslated regions (UTRs) through changes in alternative polyadenylation (APA), which are triggered by disruption of the CPSF6-containing Cleavage Factor Im (CFIm) complex. Furthermore, we find that recruitment of CPSF6 by HIV-1 cores is sufficient to perturb CPSF6 function, leading to 3\u2019 UTR shortening and subsequent transcriptional rewiring. These results suggest a model in which HIV-1 transcriptionally reprograms target cells through recruitment of CPSF6 to incoming cores to circumvent the antiviral response and enhance permissivity to infection.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013745","type":"journal-article","created":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T18:47:36Z","timestamp":1765565256000},"page":"e1013745","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Alternative polyadenylation upon CPSF6 knock-out enhances HIV-1 infection in primary T cells"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3835-5694","authenticated-orcid":true,"given":"Daphne","family":"Cornish","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn 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Viral Core","volume":"30","author":"A Selyutina","year":"2020","journal-title":"Cell Rep"},{"issue":"6","key":"ppat.1013745.ref004","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1016\/0092-8674(93)90637-6","article-title":"Human immunodeficiency virus type 1 Gag protein binds to cyclophilins A and B","volume":"73","author":"J Luban","year":"1993","journal-title":"Cell"},{"key":"ppat.1013745.ref005","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1742-4690-2-40","article-title":"TRIM5alpha selectively binds a restriction-sensitive retroviral capsid","volume":"2","author":"S Sebastian","year":"2005","journal-title":"Retrovirology"},{"issue":"14","key":"ppat.1013745.ref006","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.1073\/pnas.0509996103","article-title":"Specific recognition and accelerated uncoating of retroviral capsids by the TRIM5alpha restriction factor","volume":"103","author":"M Stremlau","year":"2006","journal-title":"Proc Natl Acad Sci 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