To determine whether HIV-1 infection induces APA and transcriptional reprogramming through recruitment of CPSF6 to capsid cores, we challenged primary CD4+ T cells from three independent donors with HIV-1 NL4–3 nef:IRES:GFP encoding either wild-type (WT) capsid or a capsid mutant virus that is deficient in CPSF6 binding (N74D). Here, CPSF6 is linked to HIV-1 infection.