{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:45:21Z","timestamp":1791315921512,"version":"4.3.1"},"update-to":[{"DOI":"10.1371\/journal.ppat.1013073","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000}}],"reference-count":87,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006492","name":"Division of Intramural Research, National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["5-R01AI143381"],"award-info":[{"award-number":["5-R01AI143381"]}],"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":["5-UM1AI164567"],"award-info":[{"award-number":["5-UM1AI164567"]}],"id":[{"id":"10.13039\/100006492","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Antiretroviral therapy (ART) has dramatically improved the clinical prognosis for people with HIV and prevents HIV transmission. However, ART does not cure HIV infection because of a persistent, latent viral reservoir in long-lived cells such as central memory CD4\n                    <jats:sup>+<\/jats:sup>\n                    T (T\n                    <jats:sub>CM<\/jats:sub>\n                    ) cells. Eliminating or preventing reservoir formation will require a better understanding of HIV-1 latency establishment. We and others have recently shown that host cell factors such as histone deacetylases (HDACs) are critical cellular factors that allow HIV-1 entry into latency. Whether HDACs interact with specific viral factors to regulate latency establishment, however, is unknown. To examine the role of individual HIV-1 accessory proteins, we constructed a panel of HIV-1 reporter strains, each expressing a single HIV-1 accessory protein, and examined them in a primary CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell latency model. Interestingly, we found that the HDAC inhibitor (HDACi) vorinostat potently enhances the effect of the HIV-1 protein Vpr in promoting HIV expression in infected cells, suggesting that Vpr possesses a cryptic transcription-promoting activity that is restricted by HDACs. This activity was dependent on a p300-binding domain of Vpr and inhibited by a selective p300 histone acetyltransferase inhibitor. Interestingly, Vpr expression also resulted in a significant increase in the proportion of infected cells with a central memory (T\n                    <jats:sub>CM<\/jats:sub>\n                    ) phenotype. Furthermore, we observed that T\n                    <jats:sub>CM<\/jats:sub>\n                    cells were more resistant to Vpr-induced apoptosis\/cell death than other CD4\n                    <jats:sup>+<\/jats:sup>\n                    T-cell subtypes, indicating that Vpr expression during reservoir formation selects for latent proviruses in T\n                    <jats:sub>CM<\/jats:sub>\n                    cells. Overall, these findings suggest that Vpr plays an important role in shaping the latent reservoir and that HIV-1 latency results, in part, from an HDAC-mediated restriction of Vpr\u2019s transcription-promoting activity. Understanding how viral factors shape the latent reservoir and how host and viral factors interact during HIV-1 latency establishment in CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells will aid in the development of new latency-targeting therapies.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1013073","type":"journal-article","created":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T17:58:56Z","timestamp":1756922336000},"page":"e1013073","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["HIV-1 accessory protein Vpr possesses a cryptic p300-dependent transcription-promoting activity that is blocked by histone deacetylases in CD4+ T cells"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7848-869X","authenticated-orcid":true,"given":"Catherine A.","family":"Lewis","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David M.","family":"Margolis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9070-7015","authenticated-orcid":true,"given":"Edward P.","family":"Browne","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,9,3]]},"reference":[{"key":"ppat.1013073.ref001","doi-asserted-by":"crossref","first-page":"294","DOI":"10.11604\/pamj.2022.42.294.35134","article-title":"Chronic comorbidities in persons living with HIV within three years of exposure to antiretroviral therapy at Pantang Antiretroviral Center in Ghana: a retrospective study","volume":"42","author":"M Kotey","year":"2022","journal-title":"Pan Afr Med J"},{"issue":"12","key":"ppat.1013073.ref002","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0243529","article-title":"Comorbidities in people living with HIV: An epidemiologic and economic analysis using a claims database in France","volume":"15","author":"V Pourcher","year":"2020","journal-title":"PLoS One"},{"issue":"11","key":"ppat.1013073.ref003","doi-asserted-by":"crossref","first-page":"6597","DOI":"10.3390\/ijerph19116597","article-title":"Voluntary counseling and testing, antiretroviral therapy access, and HIV-related stigma: global progress and challenges","volume":"19","author":"EA Armstrong-Mensah","year":"2022","journal-title":"Int J Environ Res Public Health"},{"issue":"1","key":"ppat.1013073.ref004","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1186\/s12889-023-17271-6","article-title":"Barriers and enabling structural forces affecting access to antiretroviral therapy in Nigeria","volume":"24","author":"K Oturu","year":"2024","journal-title":"BMC Public Health"},{"issue":"12","key":"ppat.1013073.ref005","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3018(22)00254-5","article-title":"Fee for home delivery and monitoring of antiretroviral therapy for HIV infection compared with standard clinic-based services in South Africa: a randomised controlled trial","volume":"9","author":"RV Barnabas","year":"2022","journal-title":"Lancet HIV"},{"issue":"6","key":"ppat.1013073.ref006","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/nm880","article-title":"Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells","volume":"9","author":"JD Siliciano","year":"2003","journal-title":"Nat Med"},{"issue":"9","key":"ppat.1013073.ref007","doi-asserted-by":"crossref","first-page":"1361","DOI":"10.1093\/infdis\/jiv218","article-title":"Precise Quantitation of the Latent HIV-1 Reservoir: Implications for Eradication Strategies","volume":"212","author":"AM Crooks","year":"2015","journal-title":"J Infect Dis"},{"issue":"17","key":"ppat.1013073.ref008","doi-asserted-by":"crossref","DOI":"10.1172\/JCI171554","article-title":"The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy","volume":"133","author":"NF McMyn","year":"2023","journal-title":"J Clin Invest"},{"issue":"12","key":"ppat.1013073.ref009","doi-asserted-by":"crossref","DOI":"10.1172\/jci.insight.128432","article-title":"Clones of infected cells arise early in HIV-infected individuals","volume":"4","author":"JM Coffin","year":"2019","journal-title":"JCI Insight"},{"issue":"24","key":"ppat.1013073.ref010","doi-asserted-by":"crossref","first-page":"13193","DOI":"10.1073\/pnas.94.24.13193","article-title":"Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy","volume":"94","author":"TW Chun","year":"1997","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5341","key":"ppat.1013073.ref011","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1126\/science.278.5341.1291","article-title":"Recovery of replication-competent HIV despite prolonged suppression of plasma viremia","volume":"278","author":"JK Wong","year":"1997","journal-title":"Science"},{"issue":"5341","key":"ppat.1013073.ref012","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1126\/science.278.5341.1295","article-title":"Identification of a Reservoir for HIV-1 in Patients on Highly Active Antiretroviral Therapy","volume":"278","author":"D Finzi","year":"1997","journal-title":"Science"},{"issue":"629","key":"ppat.1013073.ref013","doi-asserted-by":"crossref","DOI":"10.1126\/scitranslmed.abl3836","article-title":"Pembrolizumab induces HIV latency reversal in people living with HIV and cancer on antiretroviral therapy","volume":"14","author":"TS Uldrick","year":"2022","journal-title":"Sci Transl Med"},{"issue":"9","key":"ppat.1013073.ref014","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1005142","article-title":"The depsipeptide romidepsin reverses HIV-1 latency in vivo","volume":"11","author":"OS S\u00f8gaard","year":"2015","journal-title":"PLOS Pathogens"},{"issue":"7408","key":"ppat.1013073.ref015","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1038\/nature11286","article-title":"Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy","volume":"487","author":"NM Archin","year":"2012","journal-title":"Nature"},{"issue":"2","key":"ppat.1013073.ref016","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0009390","article-title":"Antiretroviral intensification and valproic acid lack sustained effect on residual HIV-1 viremia or resting CD4+ cell infection","volume":"5","author":"NM Archin","year":"2010","journal-title":"PLoS One"},{"issue":"8","key":"ppat.1013073.ref017","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1172\/JCI92684","article-title":"Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency","volume":"127","author":"NM Archin","year":"2017","journal-title":"J Clin Invest"},{"issue":"7793","key":"ppat.1013073.ref018","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1038\/s41586-020-1951-3","article-title":"Systemic HIV and SIV latency reversal via non-canonical NF-\u03baB signalling in vivo","volume":"578","author":"CC Nixon","year":"2020","journal-title":"Nature"},{"issue":"513","key":"ppat.1013073.ref019","article-title":"The replication-competent HIV-1 latent reservoir is primarily established near the time of therapy initiation","volume":"11","author":"M-R Abrahams","year":"2019","journal-title":"Sci Transl Med"},{"key":"ppat.1013073.ref020","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.18889","article-title":"Establishment and stability of the latent HIV-1 DNA reservoir","volume":"5","author":"J Brodin","year":"2016","journal-title":"Elife"},{"issue":"12","key":"ppat.1013073.ref021","doi-asserted-by":"crossref","first-page":"1617","DOI":"10.1016\/j.chembiol.2023.11.009","article-title":"A histone deacetylase network regulates epigenetic reprogramming and viral silencing in HIV-infected cells","volume":"30","author":"JJ Peterson","year":"2023","journal-title":"Cell Chem Biol"},{"issue":"5","key":"ppat.1013073.ref022","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/j.immuni.2018.04.030","article-title":"Targeting the latent reservoir for HIV-1","volume":"48","author":"S Sengupta","year":"2018","journal-title":"Immunity"},{"issue":"24","key":"ppat.1013073.ref023","doi-asserted-by":"crossref","first-page":"14070","DOI":"10.1128\/JVI.01900-14","article-title":"Quantitation of replication-competent HIV-1 in populations of resting CD4 T cells","volume":"88","author":"N Soriano-Sarabia","year":"2014","journal-title":"J Virol"},{"issue":"11","key":"ppat.1013073.ref024","first-page":"3473","article-title":"Small-molecule screening using a human primary cell model of HIV latency identifies compounds that reverse latency without cellular activation","volume":"119","author":"HC Yang","year":"2009","journal-title":"J Clin Invest"},{"issue":"2","key":"ppat.1013073.ref025","doi-asserted-by":"crossref","DOI":"10.1371\/journal.ppat.1009346","article-title":"Epigenomic characterization of latent HIV infection identifies latency regulating transcription factors","volume":"17","author":"SR Jefferys","year":"2021","journal-title":"PLoS Pathog"},{"issue":"1","key":"ppat.1013073.ref026","doi-asserted-by":"crossref","first-page":"31924","DOI":"10.1038\/srep31924","article-title":"HIV-1 Vpr reactivates latent HIV-1 provirus by inducing depletion of class I HDACs on chromatin","volume":"6","author":"B Romani","year":"2016","journal-title":"Sci Rep"},{"issue":"19","key":"ppat.1013073.ref027","doi-asserted-by":"crossref","first-page":"9724","DOI":"10.1128\/JVI.76.19.9724-9734.2002","article-title":"Human immunodeficiency virus type 1 (HIV-1) accessory protein Vpr induces transcription of the HIV-1 and glucocorticoid-responsive promoters by binding directly to p300\/CBP coactivators","volume":"76","author":"T Kino","year":"2002","journal-title":"J Virol"},{"issue":"1","key":"ppat.1013073.ref028","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1038\/nm0198-065","article-title":"HIV-1 Vpr increases viral expression by manipulation of the cell cycle: a mechanism for selection of Vpr in vivo","volume":"4","author":"WC Goh","year":"1998","journal-title":"Nat Med"},{"issue":"6","key":"ppat.1013073.ref029","doi-asserted-by":"crossref","first-page":"4686","DOI":"10.1128\/JVI.72.6.4686-4693.1998","article-title":"Vpr stimulates viral expression and induces cell killing in human immunodeficiency virus type 1-infected dividing Jurkat T cells","volume":"72","author":"XJ Yao","year":"1998","journal-title":"J Virol"},{"issue":"7","key":"ppat.1013073.ref030","doi-asserted-by":"crossref","first-page":"5422","DOI":"10.1128\/JVI.73.7.5422-5430.1999","article-title":"Cell cycle- and Vpr-mediated regulation of human immunodeficiency virus type 1 expression in primary and transformed T-cell lines","volume":"73","author":"S Gummuluru","year":"1999","journal-title":"J Virol"},{"key":"ppat.1013073.ref031","doi-asserted-by":"crossref","DOI":"10.7554\/eLife.55806","article-title":"HIV-1 Vpr induces cell cycle arrest and enhances viral gene expression by depleting CCDC137","volume":"9","author":"F Zhang","year":"2020","journal-title":"eLife"},{"issue":"2","key":"ppat.1013073.ref032","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1006\/excr.2000.5016","article-title":"Cellular distribution and karyophilic properties of matrix, integrase, and Vpr proteins from the human and simian immunodeficiency viruses","volume":"260","author":"C Depienne","year":"2000","journal-title":"Exp Cell Res"},{"issue":"2","key":"ppat.1013073.ref033","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1038\/ncb1352","article-title":"The HIV-1 Vpr and glucocorticoid receptor complex is a gain-of-function interaction that prevents the nuclear localization of PARP-1","volume":"8","author":"K Muthumani","year":"2006","journal-title":"Nat Cell Biol"},{"issue":"5544","key":"ppat.1013073.ref034","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1126\/science.1063957","article-title":"Dynamic disruptions in nuclear envelope architecture and integrity induced by HIV-1 Vpr","volume":"294","author":"CM de Noronha","year":"2001","journal-title":"Science"},{"issue":"8","key":"ppat.1013073.ref035","doi-asserted-by":"crossref","first-page":"809","DOI":"10.3390\/v12080809","article-title":"Vpr Is a VIP: HIV Vpr and Infected Macrophages Promote Viral Pathogenesis","volume":"12","author":"J Lubow","year":"2020","journal-title":"Viruses"},{"issue":"1","key":"ppat.1013073.ref036","doi-asserted-by":"crossref","first-page":"5514","DOI":"10.1038\/s41467-024-49635-w","article-title":"HIV-1 Vpr combats the PU.1-driven antiviral response in primary human macrophages","volume":"15","author":"MC Virgilio","year":"2024","journal-title":"Nat Commun"},{"key":"ppat.1013073.ref037","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1186\/1742-4690-4-84","article-title":"Localization of HIV-1 Vpr to the nuclear envelope: impact on Vpr functions and virus replication in macrophages","volume":"4","author":"G Jacquot","year":"2007","journal-title":"Retrovirology"},{"key":"ppat.1013073.ref038","first-page":"10","article-title":"Illuminating the Role of Vpr in HIV Infection of Myeloid Cells","author":"SB Nodder","year":"2019","journal-title":"Front Immunol [Internet]"},{"issue":"7","key":"ppat.1013073.ref039","doi-asserted-by":"crossref","first-page":"5579","DOI":"10.1128\/jvi.71.7.5579-5592.1997","article-title":"Human immunodeficiency virus type 1 Vpr induces apoptosis following cell cycle arrest","volume":"71","author":"SA Stewart","year":"1997","journal-title":"J Virol"},{"issue":"10","key":"ppat.1013073.ref040","doi-asserted-by":"crossref","first-page":"6304","DOI":"10.1128\/jvi.69.10.6304-6313.1995","article-title":"The human immunodeficiency virus type 1 vpr gene arrests infected T cells in the G2 + M phase of the cell cycle","volume":"69","author":"JB Jowett","year":"1995","journal-title":"J Virol"},{"issue":"4","key":"ppat.1013073.ref041","doi-asserted-by":"crossref","first-page":"2324","DOI":"10.1128\/jvi.70.4.2324-2331.1996","article-title":"Human immunodeficiency virus type 1 cell cycle control: Vpr is cytostatic and mediates G2 accumulation by a mechanism which differs from DNA damage checkpoint control","volume":"70","author":"SR Bartz","year":"1996","journal-title":"J Virol"},{"issue":"44","key":"ppat.1013073.ref042","doi-asserted-by":"crossref","first-page":"77254","DOI":"10.18632\/oncotarget.20460","article-title":"Histone deacetylase inhibitors vorinostat and panobinostat induce G1 cell cycle arrest and apoptosis in multidrug resistant sarcoma cell lines","volume":"8","author":"E Bernhart","year":"2017","journal-title":"Oncotarget"},{"issue":"9","key":"ppat.1013073.ref043","doi-asserted-by":"crossref","first-page":"585","DOI":"10.1358\/dot.2007.43.9.1112980","article-title":"Vorinostat in cutaneous T-cell lymphoma","volume":"43","author":"M Duvic","year":"2007","journal-title":"Drugs Today (Barc)"},{"issue":"2","key":"ppat.1013073.ref044","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1007\/s11060-011-0604-7","article-title":"Vorinostat modulates cell cycle regulatory proteins in glioma cells and human glioma slice cultures","volume":"105","author":"J Xu","year":"2011","journal-title":"J Neurooncol"},{"key":"ppat.1013073.ref045","article-title":"Exposure of phosphatidylserine on the surface of apoptotic lymphocytes triggers specific recognition and removal by macrophages","journal-title":"J Immunol | Am Assoc Immunol [Internet]"},{"issue":"1","key":"ppat.1013073.ref046","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/s1016-8478(23)12897-4","article-title":"Role of HIV Vpr as a regulator of apoptosis and an effector on bystander cells","volume":"21","author":"HS Moon","year":"2006","journal-title":"Mol Cells"},{"issue":"7","key":"ppat.1013073.ref047","doi-asserted-by":"crossref","first-page":"3105","DOI":"10.1128\/JVI.74.7.3105-3111.2000","article-title":"Human immunodeficiency virus type 1 vpr induces apoptosis through caspase activation","volume":"74","author":"SA Stewart","year":"2000","journal-title":"J Virol"},{"issue":"40","key":"ppat.1013073.ref048","doi-asserted-by":"crossref","first-page":"37820","DOI":"10.1074\/jbc.M205313200","article-title":"HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells","volume":"277","author":"K Muthumani","year":"2002","journal-title":"J Biol Chem"},{"issue":"9","key":"ppat.1013073.ref049","doi-asserted-by":"crossref","first-page":"5281","DOI":"10.1073\/pnas.95.9.5281","article-title":"HIV transcriptional activation by the accessory protein, VPR, is mediated by the p300 co-activator","volume":"95","author":"LK Felzien","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"27","key":"ppat.1013073.ref050","doi-asserted-by":"crossref","first-page":"23742","DOI":"10.1074\/jbc.M111.220780","article-title":"Molecular insight into how HIV-1 Vpr protein impairs cell growth through two genetically distinct pathways","volume":"286","author":"C Maudet","year":"2011","journal-title":"J Biol Chem"},{"issue":"2","key":"ppat.1013073.ref051","doi-asserted-by":"crossref","first-page":"182","DOI":"10.4161\/cc.6.2.3732","article-title":"HIV1 Vpr arrests the cell cycle by recruiting DCAF1\/VprBP, a receptor of the Cul4-DDB1 ubiquitin ligase","volume":"6","author":"E Le Rouzic","year":"2007","journal-title":"Cell Cycle"},{"issue":"5","key":"ppat.1013073.ref052","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1158\/2159-8290.CD-20-0751","article-title":"Targeting the p300\/CBP Axis in Lethal Prostate Cancer","volume":"11","author":"J Welti","year":"2021","journal-title":"Cancer Discov"},{"issue":"7674","key":"ppat.1013073.ref053","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1038\/nature24028","article-title":"Discovery of a selective catalytic p300\/CBP inhibitor that targets lineage-specific tumours","volume":"550","author":"LM Lasko","year":"2017","journal-title":"Nature"},{"issue":"12","key":"ppat.1013073.ref054","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"6","key":"ppat.1013073.ref055","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The Molecular Signatures Database Hallmark Gene Set Collection","volume":"1","author":"A Liberzon","year":"2015","journal-title":"Cell Syst"},{"issue":"4","key":"ppat.1013073.ref056","first-page":"1","article-title":"The broad impact of cell death genes on the human disease phenome","volume":"15","author":"AL Rich","year":"2024","journal-title":"Cell Death Dis"},{"issue":"38","key":"ppat.1013073.ref057","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1802028115","article-title":"Phylogenetic approach to recover integration dates of latent HIV sequences within-host","volume":"115","author":"BR Jones","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"1","key":"ppat.1013073.ref058","first-page":"11","article-title":"Identification of HIV-1 vpr product and function","volume":"3","author":"EA Cohen","year":"1990","journal-title":"J Acquir Immune Defic Syndr (1988)"},{"issue":"43","key":"ppat.1013073.ref059","doi-asserted-by":"crossref","first-page":"25564","DOI":"10.1074\/jbc.270.43.25564","article-title":"Interaction of virion protein Vpr of human immunodeficiency virus type 1 with cellular transcription factor Sp1 and trans-activation of viral long terminal repeat","volume":"270","author":"L Wang","year":"1995","journal-title":"J Biol Chem"},{"issue":"1","key":"ppat.1013073.ref060","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1084\/jem.189.1.51","article-title":"The HIV-1 virion-associated protein vpr is a coactivator of the human glucocorticoid receptor","volume":"189","author":"T Kino","year":"1999","journal-title":"J Exp Med"},{"key":"ppat.1013073.ref061","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1002\/0470862637.ch13","article-title":"Tat Acetylation: A Regulatory Switch between Early and Late Phases in HIV Transcription Elongation.","volume-title":"Reversible Protein Acetylation [Internet]","author":"M Ott","year":"2004"},{"issue":"9","key":"ppat.1013073.ref062","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.1001647","article-title":"Analysis of the RelA:CBP\/p300 interaction reveals its involvement in NF-\u03baB-driven transcription","volume":"11","author":"SP Mukherjee","year":"2013","journal-title":"PLoS Biol"},{"issue":"8","key":"ppat.1013073.ref063","doi-asserted-by":"crossref","first-page":"893","DOI":"10.1038\/nm.1972","article-title":"HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation","volume":"15","author":"N Chomont","year":"2009","journal-title":"Nat Med"},{"issue":"18","key":"ppat.1013073.ref064","doi-asserted-by":"crossref","first-page":"8059","DOI":"10.1128\/JVI.00553-16","article-title":"Establishment and reversal of HIV-1 latency in naive and central memory CD4 T cells in vitro","volume":"90","author":"JM Zerbato","year":"2016","journal-title":"J Virol"},{"issue":"5","key":"ppat.1013073.ref065","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.1128\/JVI.73.5.4101-4109.1999","article-title":"Human immunodeficiency virus type 1 (HIV-1) Vpr functions as an immediate-early protein during HIV-1 infection","volume":"73","author":"M Hrimech","year":"1999","journal-title":"J Virol"},{"issue":"6","key":"ppat.1013073.ref066","doi-asserted-by":"crossref","first-page":"3097","DOI":"10.1128\/jvi.64.6.3097-3099.1990","article-title":"Human immunodeficiency virus vpr product is a virion-associated regulatory protein","volume":"64","author":"EA Cohen","year":"1990","journal-title":"J Virol"},{"key":"ppat.1013073.ref067","article-title":"Single cell multiomic analysis of the impact of Delta-9-tetrahydrocannabinol on HIV infected CD4 T cells [Internet]","author":"M Ashokkumar","journal-title":"bioRxiv"},{"issue":"3","key":"ppat.1013073.ref068","doi-asserted-by":"crossref","DOI":"10.1128\/mBio.01369-21","article-title":"HIV-1 Vpr Induces Widespread Transcriptomic Changes in CD4 T Cells Early Postinfection","volume":"12","author":"H Bauby","year":"2021","journal-title":"mBio"},{"issue":"5","key":"ppat.1013073.ref069","article-title":"Promiscuous Targeting of Cellular Proteins by Vpr Drives Systems-Level Proteomic Remodeling in HIV-1 Infection","volume":"27","author":"EJD Greenwood","year":"2019","journal-title":"Cell Rep"},{"issue":"2","key":"ppat.1013073.ref070","doi-asserted-by":"crossref","DOI":"10.1016\/j.celrep.2022.110650","article-title":"HIV-1 Vpr drives a tissue residency-like phenotype during selective infection of resting memory T cells","volume":"39","author":"AK Reuschl","year":"2022","journal-title":"Cell Rep"},{"issue":"7","key":"ppat.1013073.ref071","doi-asserted-by":"crossref","DOI":"10.1038\/cddis.2013.248","article-title":"Altering cell death pathways as an approach to cure HIV infection","volume":"4","author":"AD Badley","year":"2013","journal-title":"Cell Death Dis"},{"issue":"8","key":"ppat.1013073.ref072","doi-asserted-by":"crossref","first-page":"4032","DOI":"10.1128\/JVI.03179-15","article-title":"Prime, Shock, and Kill: Priming CD4 T Cells from HIV Patients with a BCL-2 Antagonist before HIV Reactivation Reduces HIV Reservoir Size","volume":"90","author":"NW Cummins","year":"2016","journal-title":"J Virol"},{"issue":"10","key":"ppat.1013073.ref073","doi-asserted-by":"crossref","first-page":"1131","DOI":"10.1097\/QAD.0b013e3282fd6df4","article-title":"Valproic acid without intensified antiviral therapy has limited impact on persistent HIV infection of resting CD4 T cells","volume":"22","author":"NM Archin","year":"2008","journal-title":"AIDS"},{"issue":"6","key":"ppat.1013073.ref074","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1093\/cid\/cit813","article-title":"A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy","volume":"58","author":"AM Spivak","year":"2014","journal-title":"Clin Infect Dis"},{"issue":"19","key":"ppat.1013073.ref075","doi-asserted-by":"crossref","first-page":"7078","DOI":"10.1073\/pnas.1402873111","article-title":"Quantification of HIV-1 latency reversal in resting CD4+ T cells from patients on suppressive antiretroviral therapy","volume":"111","author":"AR Cillo","year":"2014","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ppat.1013073.ref076","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/sj.cdd.4401616","article-title":"To kill or be killed: how HIV exhausts the immune system","volume":"12","author":"M-L Gougeon","year":"2005","journal-title":"Cell Death Differ"},{"key":"ppat.1013073.ref077","unstructured":"Dissecting How CD4 T Cells Are Lost During HIV Infection - PubMed [Internet]. [cited 2025 Jun 24]. Available from: https:\/\/pubmed.ncbi.nlm.nih.gov\/26962940\/"},{"issue":"1","key":"ppat.1013073.ref078","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1084\/jem.191.1.33","article-title":"The HIV-1 Viral Protein R Induces Apoptosis via a Direct Effect on the Mitochondrial Permeability Transition Pore","volume":"191","author":"E Jacotot","year":"2000","journal-title":"J Exp Med"},{"issue":"23","key":"ppat.1013073.ref079","doi-asserted-by":"crossref","first-page":"10873","DOI":"10.1073\/pnas.91.23.10873","article-title":"Serum Vpr regulates productive infection and latency of human immunodeficiency virus type 1","volume":"91","author":"DN Levy","year":"1994","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"2","key":"ppat.1013073.ref080","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1128\/jvi.69.2.1243-1252.1995","article-title":"Extracellular Vpr protein increases cellular permissiveness to human immunodeficiency virus replication and reactivates virus from latency","volume":"69","author":"DN Levy","year":"1995","journal-title":"J Virol"},{"issue":"18","key":"ppat.1013073.ref081","doi-asserted-by":"crossref","first-page":"15118","DOI":"10.1074\/jbc.M111.312660","article-title":"Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and cellular IAP1\/2 (cIAP1\/2) in resistance to HIV-Vpr-induced apoptosis","volume":"287","author":"A Busca","year":"2012","journal-title":"J Biol Chem"},{"key":"ppat.1013073.ref082","doi-asserted-by":"crossref","first-page":"1966","DOI":"10.3389\/fimmu.2019.01966","article-title":"Blocking Formation of the Stable HIV Reservoir: A New Perspective for HIV-1 Cure","volume":"10","author":"N Goonetilleke","year":"2019","journal-title":"Front Immunol"},{"issue":"37","key":"ppat.1013073.ref083","doi-asserted-by":"crossref","first-page":"27046","DOI":"10.1074\/jbc.M703955200","article-title":"The HIV1 protein Vpr acts to promote G2 cell cycle arrest by engaging a DDB1 and Cullin4A-containing ubiquitin ligase complex using VprBP\/DCAF1 as an adaptor","volume":"282","author":"X Wen","year":"2007","journal-title":"J Biol Chem"},{"issue":"17","key":"ppat.1013073.ref084","doi-asserted-by":"crossref","first-page":"127367","DOI":"10.1016\/j.bmcl.2020.127367","article-title":"Development of a selective HDAC inhibitor aimed at reactivating the HIV latent reservoir","volume":"30","author":"DJ Clausen","year":"2020","journal-title":"Bioorg Med Chem Lett"},{"issue":"12","key":"ppat.1013073.ref085","doi-asserted-by":"crossref","first-page":"2476","DOI":"10.1021\/acsmedchemlett.0c00462","article-title":"Discovery of Highly Selective and Potent HDAC3 Inhibitors Based on a 2-Substituted Benzamide Zinc Binding Group","volume":"11","author":"J Liu","year":"2020","journal-title":"ACS Med Chem Lett"},{"issue":"6","key":"ppat.1013073.ref086","doi-asserted-by":"crossref","DOI":"10.1128\/JVI.02110-17","article-title":"Class 1-Selective Histone Deacetylase (HDAC) Inhibitors Enhance HIV Latency Reversal while Preserving the Activity of HDAC Isoforms Necessary for Maximal HIV Gene Expression","volume":"92","author":"TD Zaikos","year":"2018","journal-title":"J Virol"},{"key":"ppat.1013073.ref087","first-page":"5","article-title":"HIV-1 Vpr\u2014a still \u201cenigmatic multitasker.\u201d","author":"CA Guenzel","year":"2014","journal-title":"Front Microbiol [Internet]"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1013073","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T00:00:00Z","timestamp":1757376000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013073","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T17:54:46Z","timestamp":1757440486000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1013073"}},"subtitle":[],"editor":[{"given":"David T.","family":"Evans","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2025,9,3]]},"references-count":87,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,9,3]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1013073","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2025.03.27.645672","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,3]]}}}