biostudies-literatureTeixeira ARBill & Melinda Gates FoundationStavros Niarchos FoundationBEAT-HIV DelaneyNIAID NIH HHSREACH DelaneyNational Institutes of HealthBill and Melinda Gates FoundationRockefeller UniversityNIH HHSEinstein-Rockefeller-CUNY Center for AIDS Researche20240391https://www.ebi.ac.uk/biostudies/studies/S-EPMC11323366biostudies-literatureUnknown221(9)HIV-1 antiretroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses, leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here, we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines. Proviral gene expression was correlated to the level of endogenous gene expression under resting but not activated conditions. Notably, latent proviral promoters were 100-10,000× less active than in productively infected cells and had little or no measThe Journal of experimental medicineTranscription of HIV-1 at sites of intact latent provirus integration.PMC11323366UM1 AI164565R01 AI129795UM1 AI1266201P30AI124414-01A1INV-002705UM1 AI100663R01AI129795P30 AI124414Murdza TBittar CNussenzweig MCTeixeira ARLinden NOliveira TYCaskey MMuecksch FHuang ASSilva Santos GSJones RBJankovic MFerreira IATMfalseTranscription of HIV-1 at sites of intact latent provirus integration.HIV-1 antiretroviral therapy is highly effective but fails to eliminate a reservoir of latent proviruses, leading to a requirement for life-long treatment. How the site of integration of authentic intact latent proviruses might impact their own or neighboring gene expression or reservoir dynamics is poorly understood. Here, we report on proviral and neighboring gene transcription at sites of intact latent HIV-1 integration in cultured T cells obtained directly from people living with HIV, as well as engineered primary T cells and cell lines. Proviral gene expression was correlated to the level of endogenous gene expression under resting but not activated conditions. Notably, latent proviral promoters were 100-10,000× less active than in productively infected cells and had little or no meas2024-01-01T00:00:00Z2024 Sep2025-04-04T02:50:31.866Z2025-04-04T02:50:31.866ZS-EPMC113233663914112710.1084/jem.20240391