biostudies-literatureLuchsinger CAOU NIH HHSNIAID NIH HHSe0286525https://www.ebi.ac.uk/biostudies/studies/S-EPMC12802250biostudies-literatureUnknown17(1)HIV-1 viral core transport to the nucleus, an early infection event, triggers the redistribution of cleavage and polyadenylation specificity factors (CPSF) 5 and CPSF6 to nuclear speckles, forming puncta-like structures. CPSF5 and CPSF6 regulate alternative polyadenylation (APA), which governs approximately 70% of gene expression. APA alters the lengths of mRNA 3'-untranslated regions (3'-UTRs), which contain regulatory signals influencing RNA stability, localization, and function. We investigated whether HIV-1 infection-induced changes in CPSF5 and CPSF6 subcellular localization are accompanied by APA changes. Using two independent methodologies to assess APA in human cell lines and primary CD4+ T cells, we found that HIV-1 infection regulates APA, shaped by the interaction of CPSF6 with mBioHIV-1 infection regulates gene expression by altering alternative polyadenylation correlated with CPSF6 and CPSF5 redistribution.PMC12802250AI150455AI087390R01 AI150455R01 AI087390Luchsinger CHuang K-LYalamanchili HBertelli CWagner EJDiaz-Griffero FDai AZBalakrishnan ALorenzo-Redondo RCui BfalseHIV-1 infection regulates gene expression by altering alternative polyadenylation correlated with CPSF6 and CPSF5 redistribution.HIV-1 viral core transport to the nucleus, an early infection event, triggers the redistribution of cleavage and polyadenylation specificity factors (CPSF) 5 and CPSF6 to nuclear speckles, forming puncta-like structures. CPSF5 and CPSF6 regulate alternative polyadenylation (APA), which governs approximately 70% of gene expression. APA alters the lengths of mRNA 3'-untranslated regions (3'-UTRs), which contain regulatory signals influencing RNA stability, localization, and function. We investigated whether HIV-1 infection-induced changes in CPSF5 and CPSF6 subcellular localization are accompanied by APA changes. Using two independent methodologies to assess APA in human cell lines and primary CD4+ T cells, we found that HIV-1 infection regulates APA, shaped by the interaction of CPSF6 with 2026-01-01T00:00:00Z2026 Jan2026-06-06T14:58:10.126Z2026-06-01T03:08:04.868ZS-EPMC128022504140539010.1128/mbio.02865-25