{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:35:31Z","timestamp":1792002931546,"version":"4.4.0"},"reference-count":168,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T00:00:00Z","timestamp":1574899200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["F31AI147814"],"award-info":[{"award-number":["F31AI147814"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI124722"],"award-info":[{"award-number":["AI124722"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI116212"],"award-info":[{"award-number":["AI116212"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI147845"],"award-info":[{"award-number":["AI147845"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI126617"],"award-info":[{"award-number":["AI126617"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["AI117970"],"award-info":[{"award-number":["AI117970"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Cells that are latently infected with HIV-1 preclude an HIV-1 cure, as antiretroviral therapy does not target this latent population. HIV-1 is highly genetically diverse, with over 10 subtypes and numerous recombinant forms circulating worldwide. In spite of this vast diversity, much of our understanding of latency and latency reversal is largely based on subtype B viruses. As such, most of the development of cure strategies targeting HIV-1 are solely based on subtype B. It is currently assumed that subtype does not influence the establishment or reactivation of latent viruses. However, this has not been conclusively proven one way or the other. A better understanding of the factors that influence HIV-1 latency in all viral subtypes will help develop therapeutic strategies that can be applied worldwide. Here, we review the latest literature on subtype-specific factors that affect viral replication, pathogenesis, and, most importantly, latency and its reversal.<\/jats:p>","DOI":"10.3390\/v11121104","type":"journal-article","created":{"date-parts":[[2019,11,28]],"date-time":"2019-11-28T10:54:10Z","timestamp":1574938450000},"page":"1104","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["HIV-1 Latency and Latency Reversal: Does Subtype Matter?"],"prefix":"10.3390","volume":"11","author":[{"given":"Indra","family":"Sarabia","sequence":"first","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8800-2160","authenticated-orcid":false,"given":"Alberto","family":"Bosque","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Immunology and Tropical Medicine, The George Washington University, Washington, DC 20052, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,11,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/387183a0","article-title":"Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection","volume":"387","author":"Chun","year":"1997","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Finzi, D., Hermankova, M., Pierson, T., Carruth, L.M., Buck, C., Chaisson, R.E., Quinn, T.C., Chadwick, K., Margolick, J., and Brookmeyer, R. (1997). Identification of a Reservoir for HIV-1 in Patients on HIghly Active Antiretroviral Therapy. Science, 278.","DOI":"10.1126\/science.278.5341.1295"},{"key":"ref_3","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":"Siliciano","year":"2003","journal-title":"Nat. Med."},{"key":"ref_4","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":"Chun","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"a007096","DOI":"10.1101\/cshperspect.a007096","article-title":"HIV latency","volume":"1","author":"Siliciano","year":"2011","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a007161","DOI":"10.1101\/cshperspect.a007161","article-title":"HIV-1 antiretroviral drug therapy","volume":"2","author":"Arts","year":"2012","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.jcv.2005.09.004","article-title":"Basics of the virology of HIV-1 and its replication","volume":"34","author":"Sierra","year":"2005","journal-title":"J Clin Virol"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1038\/s41564-018-0335-z","article-title":"HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy","volume":"4","author":"Ganor","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_9","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":"Chomont","year":"2009","journal-title":"Nat. Med."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1160","DOI":"10.1128\/JVI.78.3.1160-1168.2004","article-title":"T-cell subsets that harbor human immunodeficiency virus (HIV) in vivo: Implications for HIV pathogenesis","volume":"78","author":"Brenchley","year":"2004","journal-title":"J. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9337","DOI":"10.1128\/JVI.00895-12","article-title":"Latent HIV-1 infection occurs in multiple subsets of hematopoietic progenitor cells and is reversed by NF-kappaB activation","volume":"86","author":"McNamara","year":"2012","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Venanzi Rullo, E., Cannon, L., Pinzone, M.R., Ceccarelli, M., Nunnari, G., and O\u2019Doherty, U. (2019). Genetic evidence that Naive T cells can contribute significantly to the HIV intact reservoir: Time to re-evaluate their role. Clin. Infect. Dis.","DOI":"10.1093\/cid\/ciz378"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1097\/COH.0000000000000293","article-title":"Tissue reservoirs of HIV","volume":"11","author":"Wong","year":"2016","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1126\/science.1255512","article-title":"Immunologic strategies for HIV-1 remission and eradication","volume":"345","author":"Barouch","year":"2014","journal-title":"Science"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.molmed.2015.11.004","article-title":"HIV-1 Eradication: Early Trials (and Tribulations)","volume":"22","author":"Spivak","year":"2016","journal-title":"Trends Mol. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2450","DOI":"10.3389\/fimmu.2019.02450","article-title":"Targeting Cellular and Tissue HIV Reservoirs With Toll-Like Receptor Agonists","volume":"10","author":"Macedo","year":"2019","journal-title":"Front. Immunol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1146\/annurev-med-092112-152941","article-title":"Understanding HIV latency: The road to an HIV cure","volume":"66","author":"Dahabieh","year":"2015","journal-title":"Annu. Rev. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.jinf.2012.10.026","article-title":"Implications of HIV diversity for the HIV-1 pandemic","volume":"66","author":"Hemelaar","year":"2013","journal-title":"J. Infect."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1018","DOI":"10.1080\/21645515.2016.1276138","article-title":"Progress in HIV vaccine development","volume":"13","author":"Hsu","year":"2017","journal-title":"Hum. Vaccin. Immunother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1590","DOI":"10.1056\/NEJMra0706737","article-title":"The Challenge of HIV-1 Subtype Diversity","volume":"358","author":"Taylor","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1097\/QAD.0b013e328342ff93","article-title":"Global trends in molecular epidemiology of HIV-1 during 2000-2007","volume":"25","author":"Hemelaar","year":"2011","journal-title":"AIDS"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.molmed.2011.12.001","article-title":"The origin and diversity of the HIV-1 pandemic","volume":"18","author":"Hemelaar","year":"2012","journal-title":"Trends Mol. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"W13","DOI":"10.1097\/01.aids.0000247564.73009.bc","article-title":"Global and regional distribution of HIV-1 genetic subtypes and recombinants in 2004","volume":"20","author":"Hemelaar","year":"2006","journal-title":"AIDS"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2662","DOI":"10.1128\/JCM.00880-13","article-title":"Large-scale analysis of the prevalence and geographic distribution of HIV-1 non-B variants in the United States","volume":"51","author":"Pyne","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.annepidem.2017.02.002","article-title":"Increasing HIV-1 subtype diversity in seven states, United States, 2006-2013","volume":"27","author":"Oster","year":"2017","journal-title":"Ann. Epidemiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"655","DOI":"10.3389\/fmicb.2019.00655","article-title":"Diverse Large HIV-1 Non-subtype B Clusters Are Spreading Among Men Who Have Sex With Men in Spain","volume":"10","author":"Delgado","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Yamaguchi, J., McArthur, C., Vallari, A., Sthreshley, L., Cloherty, G.A., Berg, M.G., and Rodgers, M.A. (2019). Complete genome sequence of CG-0018a-01 establishes HIV-1 subtype L. J. Acquir. Immune Defic. Syndr.","DOI":"10.1097\/QAI.0000000000002246"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1097\/00002030-199905280-00005","article-title":"Similar rate of disease progression among individuals infected with HIV-1 genetic subtypes A-D","volume":"13","author":"Alaeus","year":"1999","journal-title":"AIDS"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1097\/00002030-199910010-00020","article-title":"Clinical disease associated with HIV-1 subtype B\u2019 and E infection among 2104 patients in Thailand","volume":"13","author":"Amornkul","year":"1999","journal-title":"AIDS"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0140-6736(05)60982-8","article-title":"African HIV-1 subtype C and rate of progression among Ethiopian immigrants in Israel","volume":"349","author":"Galai","year":"1997","journal-title":"Lancet"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1097\/QAI.0b013e3181c98fc0","article-title":"HIV-1 viral subtype differences in the rate of CD4+ T-cell decline among HIV seroincident antiretroviral naive persons in Rakai district, Uganda","volume":"54","author":"Kiwanuka","year":"2010","journal-title":"J. Acquir. Immune. Defic. Syndr."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1177","DOI":"10.1086\/512682","article-title":"HIV-1 subtype D infection is associated with faster disease progression than subtype A in spite of similar plasma HIV-1 loads","volume":"195","author":"Baeten","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1244","DOI":"10.1086\/340130","article-title":"Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda","volume":"185","author":"Kaleebu","year":"2002","journal-title":"J. Infect. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Ssemwanga, D., Nsubuga, R.N., Mayanja, B.N., Lyagoba, F., Magambo, B., Yirrell, D., Van der Paal, L., Grosskurth, H., and Kaleebu, P. (2013). Effect of HIV-1 subtypes on disease progression in rural Uganda: A prospective clinical cohort study. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0071768"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1086\/499952","article-title":"Different rates of disease progression of HIV type 1 infection in Tanzania based on infecting subtype","volume":"42","author":"Vasan","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.ebiom.2016.10.014","article-title":"Infecting HIV-1 Subtype Predicts Disease Progression in Women of Sub-Saharan Africa","volume":"13","author":"Venner","year":"2016","journal-title":"EBioMedicine"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1097\/QAD.0000000000000012","article-title":"Disease progression by infecting HIV-1 subtype in a seroconverter cohort in sub-Saharan Africa","volume":"27","author":"Amornkul","year":"2013","journal-title":"AIDS"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1086\/314557","article-title":"Human immunodeficiency virus type 1 subtypes differ in disease progression","volume":"179","author":"Kanki","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1146\/annurev.immunol.17.1.657","article-title":"Chemokine receptors as HIV-1 coreceptors: Roles in viral entry, tropism, and disease","volume":"17","author":"Berger","year":"1999","journal-title":"Annu. Rev. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1084\/jem.185.4.621","article-title":"Change in coreceptor use correlates with disease progression in HIV-1--infected individuals","volume":"185","author":"Connor","year":"1997","journal-title":"J. Exp. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1089\/088922204322749567","article-title":"The CCR5 and CXCR4 Coreceptors\u2014 Central to Understanding the Transmission and Pathogenesis of Human Immunodeficiency VIrus Type 1 Infection","volume":"20","author":"Moore","year":"2004","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/1742-4690-7-23","article-title":"Frequent CXCR4 tropism of HIV-1 subtype A and CRF02_AG during late-stage disease--indication of an evolving epidemic in West Africa","volume":"7","author":"Esbjornsson","year":"2010","journal-title":"Retrovirology"},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Beitari, S., Wang, Y., Liu, S.L., and Liang, C. (2019). HIV-1 Envelope Glycoprotein at the Interface of Host Restriction and Virus Evasion. Viruses, 11.","DOI":"10.3390\/v11040311"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1089\/aid.2008.0219","article-title":"Appreciating HIV type 1 diversity: Subtype differences in Env","volume":"25","author":"Lynch","year":"2009","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1126\/science.1118398","article-title":"Structure of a V3-containing HIV-1 gp120 core","volume":"310","author":"Huang","year":"2005","journal-title":"Science"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1126\/science.1905842","article-title":"Identification of the envelope V3 loop as the primary determinant of cell tropism in HIV-1","volume":"253","author":"Hwang","year":"1991","journal-title":"Science"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3852","DOI":"10.1128\/JVI.76.8.3852-3864.2002","article-title":"Variability in the human immunodeficiency virus type 1 gp120 Env protein linked to phenotype-associated changes in the V3 loop","volume":"76","author":"Hoffman","year":"2002","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1080\/003655400458695","article-title":"Significance of HIV-1 genetic subtypes","volume":"32","author":"Alaeus","year":"2000","journal-title":"Scand. J. Infect. Dis."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1006\/viro.1997.8980","article-title":"Differences in chemokine coreceptor usage between genetic subtypes of HIV-1","volume":"241","author":"Tscherning","year":"1998","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.virol.2006.07.030","article-title":"Genetic characteristics of the V3 region associated with CXCR4 usage in HIV-1 subtype C isolates","volume":"356","author":"Coetzer","year":"2006","journal-title":"Virology"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1089\/aid.2006.22.703","article-title":"Distinct sequence patterns characterize the V3 region of HIV type 1 gp120 from subtypes A and C","volume":"22","author":"Felsovalyi","year":"2006","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"7885","DOI":"10.1128\/JVI.00218-07","article-title":"Coreceptor tropism in human immunodeficiency virus type 1 subtype D: High prevalence of CXCR4 tropism and heterogeneous composition of viral populations","volume":"81","author":"Huang","year":"2007","journal-title":"J. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1186\/1758-2652-15-2","article-title":"The epidemiology and clinical correlates of HIV-1 co-receptor tropism in non-subtype B infections from India, Uganda and South Africa","volume":"15","author":"Ataher","year":"2012","journal-title":"J. Int. AIDS Soc."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"768","DOI":"10.1038\/383768a0","article-title":"HIV-1 subtype and second-receptor use","volume":"383","author":"Zhang","year":"1996","journal-title":"Nature"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1093\/infdis\/jiw172","article-title":"Diversity and Tropism of HIV-1 Rebound Virus Populations in Plasma Level After Treatment Discontinuation","volume":"214","author":"Bednar","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Pardons, M., Baxter, A.E., Massanella, M., Pagliuzza, A., Fromentin, R., Dufour, C., Leyre, L., Routy, J.P., Kaufmann, D.E., and Chomont, N. (2019). Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007619"},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Grau-Exposito, J., Luque-Ballesteros, L., Navarro, J., Curran, A., Burgos, J., Ribera, E., Torrella, A., Planas, B., Badia, R., and Martin-Castillo, M. (2019). Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007991"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1093\/nar\/28.3.663","article-title":"A compilation of cellular transcription factor interactions with the HIV-1 LTR promoter","volume":"28","author":"Pereira","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/S1074-7613(00)80326-X","article-title":"The T cell activation factor NF-ATc positively regulates HIV-1 replication and gene expression in T cells","volume":"6","author":"Kinoshita","year":"1997","journal-title":"Immunity"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1182\/blood-2008-07-168393","article-title":"Induction of HIV-1 latency and reactivation in primary memory CD4+ T cells","volume":"113","author":"Bosque","year":"2009","journal-title":"Blood"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6043","DOI":"10.1128\/JVI.02074-06","article-title":"Sustained induction of NF-kappa B is required for efficient expression of latent human immunodeficiency virus type 1","volume":"81","author":"Williams","year":"2007","journal-title":"J. Virol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"902","DOI":"10.3390\/v5030902","article-title":"Lost in transcription: Molecular mechanisms that control HIV latency","volume":"5","author":"Taube","year":"2013","journal-title":"Viruses"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1016\/j.celrep.2017.01.022","article-title":"Benzotriazoles Reactivate Latent HIV-1 through Inactivation of STAT5 SUMOylation","volume":"18","author":"Bosque","year":"2017","journal-title":"Cell Rep."},{"key":"ref_64","first-page":"328","article-title":"Reactivation of latent HIV-1 by new semi-synthetic ingenol esters","volume":"462\u2013463","author":"Bartholomeeusen","year":"2014","journal-title":"Virology"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"26","DOI":"10.2174\/1874357900701010026","article-title":"Heterogeneity of signal transducer and activator of transcription binding sites in the long-terminal repeats of distinct HIV-1 subtypes","volume":"1","author":"Crotti","year":"2007","journal-title":"Open Virol. J."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3740","DOI":"10.1128\/JVI.74.8.3740-3751.2000","article-title":"Functional differences between the long terminal repeat transcriptional promoters of human immunodeficiency virus type 1 subtypes A through G","volume":"74","author":"Jeeninga","year":"2000","journal-title":"J. Virol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1089\/aid.2007.0152","article-title":"Genetic and functional characterization of the LTR of HIV-1 subtypes A and C circulating in India","volume":"23","author":"Rodriguez","year":"2007","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1006\/viro.2001.1397","article-title":"Differential regulation of HIV-1 clade-specific B, C, and E long terminal repeats by NF-kappaB and the Tat transactivator","volume":"296","author":"Roof","year":"2002","journal-title":"Virology"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"3675","DOI":"10.1128\/JVI.78.7.3675-3683.2004","article-title":"Human immunodeficiency virus type 1 subtypes have a distinct long terminal repeat that determines the replication rate in a host-cell-specific manner","volume":"78","author":"Jeeninga","year":"2004","journal-title":"J. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"8657","DOI":"10.1128\/jvi.71.11.8657-8665.1997","article-title":"Divergent transcriptional regulation among expanding human immunodeficiency virus type 1 subtypes","volume":"71","author":"Montano","year":"1997","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5958","DOI":"10.1128\/JVI.00161-10","article-title":"Combinatorial latency reactivation for HIV-1 subtypes and variants","volume":"84","author":"Burnett","year":"2010","journal-title":"J. Virol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"34532","DOI":"10.1038\/srep34532","article-title":"The variances of Sp1 and NF-kappaB elements correlate with the greater capacity of Chinese HIV-1 B\u2032-LTR for driving gene expression","volume":"6","author":"Qu","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"44714","DOI":"10.1074\/jbc.M112.397158","article-title":"Multiple NF-kappaB sites in HIV-1 subtype C long terminal repeat confer superior magnitude of transcription and thereby the enhanced viral predominance","volume":"287","author":"Bachu","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1331","DOI":"10.1128\/JVI.73.2.1331-1340.1999","article-title":"Evolution of the human immunodeficiency virus type 1 long terminal repeat promoter by conversion of an NF-kappaB enhancer element into a GABP binding site","volume":"73","author":"Verhoef","year":"1999","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1038\/sj.emboj.7600900","article-title":"NF-\u03baB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional intiation","volume":"24","author":"Williams","year":"2006","journal-title":"EMBO J."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1186\/1742-4690-8-73","article-title":"Latency profiles of full length HIV-1 molecular clone variants with a subtype specific promoter","volume":"8","author":"Pollakis","year":"2011","journal-title":"Retrovirology"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"2264","DOI":"10.1128\/JVI.01594-12","article-title":"An AP-1 binding site in the enhancer\/core element of the HIV-1 promoter controls the ability of HIV-1 to establish latent infection","volume":"87","author":"Duverger","year":"2013","journal-title":"J. Virol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"4716","DOI":"10.1128\/JVI.03478-12","article-title":"A doubly fluorescent HIV-1 reporter shows that the majority of integrated HIV-1 is latent shortly after infection","volume":"87","author":"Dahabieh","year":"2013","journal-title":"J. Virol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1126\/science.1254194","article-title":"HIV latency. Specific HIV integration sites are linked to clonal expansion and persistence of infected cells","volume":"345","author":"Maldarelli","year":"2014","journal-title":"Science"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1126\/science.1256304","article-title":"HIV latency. Proliferation of cells with HIV integrated into cancer genes contributes to persistent infection","volume":"345","author":"Wagner","year":"2014","journal-title":"Science"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"320","DOI":"10.1093\/jac\/dkp423","article-title":"Integrase variability and susceptibility to HIV integrase inhibitors: Impact of subtypes, antiretroviral experience and duration of HIV infection","volume":"65","author":"Garrido","year":"2010","journal-title":"J Antimicrob. Chemother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1093\/jac\/dkg079","article-title":"Impact of clade diversity on HIV-1 virulence, antiretroviral drug sensitivity and drug resistance","volume":"51","author":"Spira","year":"2003","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_83","first-page":"17","article-title":"Characterization and structural analysis of HIV-1 integrase conservation","volume":"11","author":"Malet","year":"2009","journal-title":"AIDS Rev."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.chom.2014.09.016","article-title":"HIV-1 integrase variants retarget viral integration and are associated with disease progression in a chronic infection cohort","volume":"16","author":"Demeulemeester","year":"2014","journal-title":"Cell Host. Microbe"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1146\/annurev.biochem.67.1.1","article-title":"HIV-1: Fifteen proteins and an RNA","volume":"67","author":"Frankel","year":"1998","journal-title":"Annu. Rev. Biochem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"7792","DOI":"10.1074\/jbc.M313093200","article-title":"Vif overcomes the innate antiviral activity of APOBEC3G by promoting its degradation in the ubiquitin-proteasome pathway","volume":"279","author":"Mehle","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1159\/000348513","article-title":"HIV-1 subtype variability in Vif derived from molecular clones affects APOBEC3G-mediated host restriction","volume":"56","author":"Lisovsky","year":"2013","journal-title":"Intervirology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.chom.2017.03.008","article-title":"Defective HIV-1 Proviruses Are Expressed and Can Be Recognized by Cytotoxic T Lymphocytes, which Shape the Proviral Landscape","volume":"21","author":"Pollack","year":"2017","journal-title":"Cell Host. Microbe"},{"key":"ref_89","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":"Romani","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1006\/viro.2000.0650","article-title":"Establishment of latent HIV-1 infection of resting CD4(+) T lymphocytes does not require inactivation of Vpr","volume":"278","author":"Shen","year":"2000","journal-title":"Virology"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1832","DOI":"10.1097\/QAD.0b013e328277f16b","article-title":"Vpr from HIV-1 subtypes B and C exhibit significant differences in their ability to transactivate LTR-mediated gene expression and also in their ability to promote apoptotic DNA ladder formation","volume":"21","author":"Bano","year":"2007","journal-title":"Aids"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"171","DOI":"10.2174\/156652407780059177","article-title":"Mechanisms of CD4 downregulation by the Nef and Vpu proteins of primate immunodeficiency viruses","volume":"7","author":"Lindwasser","year":"2007","journal-title":"Curr. Mol. Med."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Langer, S., Hammer, C., Hopfensperger, K., Klein, L., Hotter, D., De Jesus, P.D., Herbert, K.M., Pache, L., Smith, N., and van der Merwe, J.A. (2019). HIV-1 Vpu is a potent transcriptional suppressor of NF-kappaB-elicited antiviral immune responses. Elife, 8.","DOI":"10.7554\/eLife.41930"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1089\/088922299311673","article-title":"Genetic characterization of the nef gene from human immunodeficiency virus type 1 group M strains representing genetic subtypes A, B, C, E, F, G, and H","volume":"15","author":"Saragosti","year":"1999","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Mann, J.K., Byakwaga, H., Kuang, X.T., Le, A.Q., Brumme, C.J., Mwimanzi, P., Omarjee, S., Martin, E., Lee, G.Q., and Baraki, B. (2013). Ability fo HIV-1 Nef to downregulate CD4 and HLA class I differs among viral subtypes. Retrovirology, 10.","DOI":"10.1186\/1742-4690-10-100"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1186\/s12985-015-0429-7","article-title":"Genetic determinants of Nef-mediated CD4 and HLA class I down-regulation differences between HIV-1 subtypes B and C","volume":"12","author":"Mann","year":"2015","journal-title":"Virol. J."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5289","DOI":"10.4049\/jimmunol.155.11.5289","article-title":"Extracellular Nef protein regulates productive HIV-1 infection from latency","volume":"155","author":"Fujinaga","year":"1995","journal-title":"J. Immunol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.chom.2008.08.013","article-title":"HIV Nef enhances Tat-mediated viral transcription through a hnRNP-K-nucleated signaling complex","volume":"4","author":"Wolf","year":"2008","journal-title":"Cell Host. Microbe"},{"key":"ref_99","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":"Levy","year":"1995","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Mousseau, G., Aneja, R., Clementz, M.A., Mediouni, S., Lima, N.S., Haregot, A., Kessing, C.F., Jablonski, J.A., Thenin-Houssier, S., and Nagarsheth, N. (2019). Resistance to the Tat Inhibitor Didehydro-Cortistatin A Is Mediated by Heightened Basal HIV-1 Transcription. MBio, 10.","DOI":"10.1128\/mBio.01750-18"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.chom.2012.05.016","article-title":"An analog of the natural steroidal alkaloid cortistatin A potently suppresses Tat-dependent HIV transcription","volume":"12","author":"Mousseau","year":"2012","journal-title":"Cell Host. Microbe"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"e00465","DOI":"10.1128\/mBio.00465-15","article-title":"The Tat Inhibitor Didehydro-Cortistatin A Prevents HIV-1 Reactivation from Latency","volume":"6","author":"Mousseau","year":"2015","journal-title":"MBio"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.virol.2011.06.024","article-title":"HIV latency is influenced by regions of the viral genome outside of the long terminal repeats and regulatory genes","volume":"417","author":"Marsden","year":"2011","journal-title":"Virology"},{"key":"ref_104","first-page":"S5","article-title":"Heterogeneity of HIV-1 and HIV-2","volume":"9","author":"Korber","year":"1995","journal-title":"AIDS"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1186\/1742-4690-7-85","article-title":"Subtype-associated differences in HIV-1 reverse transcription affect the viral replication","volume":"7","author":"Iordanskly","year":"2010","journal-title":"Retrovirology"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"1308","DOI":"10.1093\/cid\/cix478","article-title":"Reduced Frequency of Cells Latently Infected With Replication-Competent Human Immunodeficiency Virus-1 in Virally Suppressed Individuals Living in Rakai, Uganda","volume":"65","author":"Prodger","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Omondi, F.H., Chandrarathna, S., Mujib, S., Brumme, C.J., Jin, S.W., Sudderuddin, H., Miller, R.L., Rahimi, A., Laeyendecker, O., and Bonner, P. (2019). HIV Subtype and Nef-Mediated Immune Evasion Function Correlate with Viral Reservoir Size in Early-Treated Individuals. J. Virol., 93.","DOI":"10.1128\/JVI.01832-18"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.1038\/s41467-019-10884-9","article-title":"Determinants of HIV-1 reservoir size and long-term dynamics during suppressive ART","volume":"10","author":"Bachmann","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1097\/COH.0000000000000122","article-title":"How does the timing of antiretroviral therapy initiation in acute infection affect HIV reservoirs?","volume":"10","author":"Ananworanich","year":"2015","journal-title":"Curr. Opin. HIV AIDS"},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"9523","DOI":"10.1073\/pnas.1120248109","article-title":"Immediate antiviral therapy appears to restrict resting CD4+ cell HIV-1 infection without accelerating the decay of latent infection","volume":"109","author":"Archin","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Eriksson, S., Graf, E.H., Dahl, V., Strain, M.C., Yukl, S.A., Lysenko, E.S., Bosch, R.J., Lai, J., Chioma, S., and Emad, F. (2013). Comparative analysis of measures of viral reservoirs in HIV-1 eradication studies. PLoS Pathog., 9.","DOI":"10.1371\/journal.ppat.1003174"},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1016\/j.cell.2013.09.020","article-title":"Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure","volume":"155","author":"Ho","year":"2013","journal-title":"Cell"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"1043","DOI":"10.1038\/nm.4156","article-title":"Defective proviruses rapidly accumulate during acute HIV-1 infection","volume":"22","author":"Bruner","year":"2016","journal-title":"Nat. Med."},{"key":"ref_114","doi-asserted-by":"crossref","unstructured":"Yue, F.Y., Cohen, J.C., Ho, M., Rahman, A., Liu, J., Mujib, S., Saiyed, A., Hundal, S., Khozin, A., and Bonner, P. (2017). HIV-Specific Granzyme B-Secreting but Not Gamma Interferon-Secreting T Cells Are Associated with Reduced Viral Reservoirs in Early HIV Infection. J. Virol., 91.","DOI":"10.1128\/JVI.02233-16"},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/QAI.0b013e3182a1bc81","article-title":"Susceptibility to CD8 T-cell-mediated killing influences the reservoir of latently HIV-1-infected CD4 T cells","volume":"65","author":"Yang","year":"2014","journal-title":"J. Acquir. Immune. Defic. Syndr."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Vabret, N., Bailly-Bechet, M., Najburg, V., Muller-Trutwin, M., Verrier, B., and Tangy, F. (2012). The biased nucleotide composition of HIV-1 triggers type I interferon response and correlates with subtype D increased pathogenicity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0033502"},{"key":"ref_117","doi-asserted-by":"crossref","unstructured":"Kiguoya, M.W., Mann, J.K., Chopera, D., Gounder, K., Lee, G.Q., Hunt, P.W., Martin, J.N., Ball, T.B., Kimani, J., and Brumme, Z.L. (2017). Subtype-Specific Differences in Gag-Protease-Driven Replication Capacity Are Consistent with Intersubtype Differences in HIV-1 Disease Progression. J. Virol., 91.","DOI":"10.1128\/JVI.00253-17"},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.virol.2019.02.011","article-title":"Nef-mediated inhibition of NFAT following TCR stimulation differs between HIV-1 subtypes","volume":"531","author":"Naidoo","year":"2019","journal-title":"Virology"},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Ojwach, D.B.A., MacMillan, D., Reddy, T., Novitsky, V., Brumme, Z.L., Brockman, M.A., Ndung\u2019u, T., and Mann, J.K. (2018). Pol-Driven Replicative Capacity Impacts Disease Progression in HIV-1 Subtype C Infection. J. Virol., 92.","DOI":"10.1128\/JVI.00811-18"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.chom.2017.12.004","article-title":"Getting the \u201cKill\u201d into \u201cShock and Kill\u201d: Strategies to Eliminate Latent HIV","volume":"23","author":"Kim","year":"2018","journal-title":"Cell Host. Microbe"},{"key":"ref_121","doi-asserted-by":"crossref","unstructured":"Spivak, A.M., and Planelles, V. (2018). Novel Latency Reversal Agents for HIV-1 Cure. Annu. Rev. Med.","DOI":"10.1146\/annurev-med-052716-031710"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"S111","DOI":"10.1093\/infdis\/jiw618","article-title":"Proviral Latency, Persistent Human Immunodeficiency Virus Infection, and the Development of Latency Reversing Agents","volume":"215","author":"Margolis","year":"2017","journal-title":"J. Infect. Dis."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"968","DOI":"10.1099\/vir.0.059642-0","article-title":"Interplay between viral Tat protein and c-Jun transcription factor in controlling LTR promoter activity in different human immunodeficiency virus type I subtypes","volume":"95","author":"Derking","year":"2014","journal-title":"J. Gen. Virol."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"7046","DOI":"10.1128\/JVI.00308-16","article-title":"Functional Incompatibility between the Generic NF-kappaB Motif and a Subtype-Specific Sp1III Element Drives the Formation of the HIV-1 Subtype C Viral Promoter","volume":"90","author":"Verma","year":"2016","journal-title":"J. Virol."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1089\/aid.2014.0199","article-title":"Targeting NF-kappaB signaling with protein kinase C agonists as an emerging strategy for combating HIV latency","volume":"31","author":"Jiang","year":"2015","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Christian, F., Smith, E.L., and Carmody, R.J. (2016). The Regulation of NF-kappaB Subunits by Phosphorylation. Cells, 5.","DOI":"10.3390\/cells5010012"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1172\/JCI11918","article-title":"Hostile takeovers: Viral appropriation of the NF-\u03baB pathway","volume":"107","author":"Hiscott","year":"2001","journal-title":"J. Clin. Investig."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"3006","DOI":"10.1182\/blood.V98.10.3006","article-title":"Prostratin: Activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART","volume":"98","author":"Kulkosky","year":"2001","journal-title":"Blood"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"42008","DOI":"10.1074\/jbc.M402124200","article-title":"Prostratin antagonizes HIV latency by activating NF-kappaB","volume":"279","author":"Williams","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Mehla, R., Bivalkar-Mehla, S., Zhang, R., Handy, I., Albrecht, H., Giri, S., Nagarkatti, P., Nagarkatti, M., and Chauhan, A. (2010). Bryostatin modulates latent HIV-1 infection via PKC and AMPK signaling but inhibits acute infection in a receptor independent manner. PLoS ONE, 5.","DOI":"10.1371\/journal.pone.0011160"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"5984","DOI":"10.1128\/AAC.01077-15","article-title":"Ex Vivo Bioactivity and HIV-1 Latency Reversal by Ingenol Dibenzoate and Panobinostat in Resting CD4(+) T Cells from Aviremic Patients","volume":"59","author":"Spivak","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1089\/aid.2015.0106","article-title":"Modeling HIV-1 Latency in Primary T Cells Using a Replication-Competent Virus","volume":"32","author":"Martins","year":"2016","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"39032","DOI":"10.1038\/srep39032","article-title":"In vitro effects of the small-molecule protein kinase C agonists on HIV latency reactivation","volume":"6","author":"Brogdon","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Jiang, G., Maverakis, E., Cheng, M.Y., Elsheikh, M.M., Deleage, C., Mendez-Lagares, G., Shimoda, M., Yukl, S.A., Hartigan-O\u2019Connor, D.J., and Thompson, G.R. (2019). Disruption of latent HIV in vivo during the clearance of actinic keratosis by ingenol mebutate. JCI Insight, 4.","DOI":"10.1172\/jci.insight.126027"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1038\/35100529","article-title":"Toll-like receptors and innate immunity","volume":"1","author":"Medzhitov","year":"2001","journal-title":"Nat. Rev. Immunol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"79","DOI":"10.3389\/fimmu.2014.00079","article-title":"TLR Agonists as Modulators of the Innate Immune Response and Their Potential as Agents Against Infectious Disease","volume":"5","author":"Mifsud","year":"2014","journal-title":"Front. Immunol."},{"key":"ref_137","doi-asserted-by":"crossref","unstructured":"Macedo, A.B., Novis, C.L., De Assis, C.M., Sorensen, E.S., Moszczynski, P., Huang, S.-h., Ren, Y., Spivak, A.M., Jones, R.B., and Planelles, V. (2018). Dual TLR2 and TLR7 agonists as HIV latency-reversing agents. JCI Insight, 3.","DOI":"10.1172\/jci.insight.122673"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1186\/1742-4690-10-119","article-title":"Reactivation of latent HIV-1 in central memory CD4(+) T cells through TLR-1\/2 stimulation","volume":"10","author":"Novis","year":"2013","journal-title":"Retrovirology"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"4441","DOI":"10.1128\/JVI.00222-16","article-title":"A Novel Toll-Like Receptor 9 Agonist, MGN1703, Enhances HIV-1 Transcription and NK Cell-Mediated Inhibition of HIV-1-Infected Autologous CD4+ T Cells","volume":"90","author":"Offersen","year":"2016","journal-title":"J. Virol."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Tsai, A., Irrinki, A., Kaur, J., Cihlar, T., Kukolj, G., Sloan, D.D., and Murry, J.P. (2017). Toll-Like Receptor 7 Agonist GS-9620 Induces HIV Expression and HIV-Specific Immunity in Cells from HIV-Infected Individuals on Suppressive Antiretroviral Therapy. J. Virol., 91.","DOI":"10.1128\/JVI.02166-16"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.chom.2015.08.009","article-title":"BIRC2\/cIAP1 Is a Negative Regulator of HIV-1 Transcription and Can Be Targeted by Smac Mimetics to Promote Reversal of Viral Latency","volume":"18","author":"Pache","year":"2015","journal-title":"Cell Host. Microbe"},{"key":"ref_142","doi-asserted-by":"crossref","unstructured":"Sampey, G.C., Irlbeck, D.M., Browne, E.P., Kanke, M., McAllister, A.B., Ferris, R.G., Brehm, J.H., Favre, D., Routy, J.P., and Jones, C.D. (2018). The SMAC Mimetic AZD5582 is a Potent HIV Latency Reversing Agent. BioRxic Prepr.","DOI":"10.1101\/312447"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/S2055-6640(20)30280-6","article-title":"Highlights from the Fourth Biennial Strategies for an HIV Cure Meeting, 10-12 October 2018, Bethesda, MD, USA","volume":"5","author":"Kuo","year":"2019","journal-title":"J. Virus. Erad."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"554","DOI":"10.2174\/157016211798998736","article-title":"Control of HIV latency by epigenetic and non-epigenetic mechanisms","volume":"9","author":"Mbonye","year":"2011","journal-title":"Curr. HIV Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"FSO372","DOI":"10.4155\/fsoa-2018-0115","article-title":"Bromodomain and extra-terminal motif inhibitors: A review of preclinical and clinical advances in cancer therapy","volume":"5","author":"Alqahtani","year":"2019","journal-title":"Future Sci. OA"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1038\/nrd2133","article-title":"Anticancer activities of histone deacetylase inhibitors","volume":"5","author":"Bolden","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1016\/j.bcp.2016.08.009","article-title":"Epigenetic blockade of neoplastic transformation by bromodomain and extra-terminal (BET) domain protein inhibitor JQ-1","volume":"117","author":"Zhang","year":"2016","journal-title":"Biochem. Pharmacol."},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1093\/nar\/gks976","article-title":"The BET bromodomain inhibitor JQ1 activates HIV latency through antagonizing Brd4 inhibition of Tat-transactivation","volume":"41","author":"Li","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"16646","DOI":"10.1038\/s41598-017-16816-1","article-title":"BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency","volume":"7","author":"Lu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","first-page":"117","DOI":"10.15252\/emmm.201505557","article-title":"Sequential treatment with 5-aza-2\u2032-deoxycytidine and deacetylase inhibitors reactivates HIV-1","volume":"8","author":"Bouchat","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"1473","DOI":"10.1097\/QAD.0b013e32835535f5","article-title":"Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4(+) T cells from HIV-1-infected HAART-treated patients","volume":"26","author":"Bouchat","year":"2012","journal-title":"AIDS"},{"key":"ref_152","doi-asserted-by":"crossref","unstructured":"Elliott, J.H., Wightman, F., Solomon, A., Ghneim, K., Ahlers, J., Cameron, M.J., Smith, M.Z., Spelman, T., McMahon, J., and Velayudham, P. (2014). Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004473"},{"key":"ref_153","doi-asserted-by":"crossref","unstructured":"Zaikos, T.D., Painter, M.M., Sebastian Kettinger, N.T., Terry, V.H., and Collins, K.L. (2018). Class 1-Selective Histone Deacetylase (HDAC) Inhibitors Enhance HIV Latency Reversal while Preserving the Activity of HDAC Isoforms Necessary for Maximal HIV Gene Expression. J. Virol., 92.","DOI":"10.1128\/JVI.02110-17"},{"key":"ref_154","doi-asserted-by":"crossref","first-page":"16538","DOI":"10.1074\/jbc.M110.103531","article-title":"Involvement of histone H3 lysine 9 (H3K9) methyltransferase G9a in the maintenance of HIV-1 latency and its reactivation by BIX01294","volume":"285","author":"Imai","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1189\/jlb.0312165","article-title":"BET bromodomain inhibition as a novel strategy for reactivation of HIV-1","volume":"92","author":"Banerjee","year":"2012","journal-title":"J. Leukoc. Biol."},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"36609","DOI":"10.1074\/jbc.M112.410746","article-title":"Bromodomain and extra-terminal (BET) bromodomain inhibition activate transcription via transient release of positive transcription elongation factor b (P-TEFb) from 7SK small nuclear ribonucleoprotein","volume":"287","author":"Bartholomeeusen","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_157","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":"Archin","year":"2012","journal-title":"Nature"},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.1097\/QAD.0b013e3282fd6ddc","article-title":"Prolonged valproic acid treatment does not reduce the size of the latent HIV reservoir","volume":"22","author":"Lamine","year":"2008","journal-title":"AIDS"},{"key":"ref_159","doi-asserted-by":"crossref","first-page":"5390","DOI":"10.1128\/JVI.00040-12","article-title":"Paucity of HIV DNA methylation in latently infected, resting CD4+ T cells from infected individuals receiving antiretroviral therapy","volume":"86","author":"Blazkova","year":"2012","journal-title":"J. Virol."},{"key":"ref_160","doi-asserted-by":"crossref","unstructured":"Blazkova, J., Trejbalova, K., Gondois-Rey, F., Halfon, P., Philibert, P., Guiguen, A., Verdin, E., Olive, D., Van Lint, C., and Hejnar, J. (2009). CpG methylation controls reactivation of HIV from latency. PLoS Pathog., 5.","DOI":"10.1371\/journal.ppat.1000554"},{"key":"ref_161","doi-asserted-by":"crossref","unstructured":"Yukl, S.A., Kaiser, P., Kim, P., Telwatte, S., Joshi, S.K., Vu, M., Lampiris, H., and Wong, J.K. (2018). HIV latency in isolated patient CD4(+) T cells may be due to blocks in HIV transcriptional elongation, completion, and splicing. Sci. Transl. Med., 10.","DOI":"10.1126\/scitranslmed.aap9927"},{"key":"ref_162","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1128\/MCB.20.8.2629-2634.2000","article-title":"P-TEFb, a cyclin-dependent kinase controlling elongation by RNA polymerase II","volume":"20","author":"Price","year":"2000","journal-title":"Mol. Cell. Biol."},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.molcel.2006.06.014","article-title":"Controlling the elongation phase of transcription with P-TEFb","volume":"23","author":"Peterlin","year":"2006","journal-title":"Mol. Cell."},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"13690","DOI":"10.1073\/pnas.0705053104","article-title":"Conserved P-TEFb-interacting domain of BRD4 inhibits HIV transcription","volume":"104","author":"Bisgrove","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1038\/nm.3489","article-title":"New ex vivo approaches distinguish effective and ineffective single agents for reversing HIV-1 latency in vivo","volume":"20","author":"Bullen","year":"2014","journal-title":"Nat. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1901","DOI":"10.1172\/JCI80142","article-title":"Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations","volume":"125","author":"Laird","year":"2015","journal-title":"J. Clin. Invest."},{"key":"ref_167","doi-asserted-by":"crossref","unstructured":"Bui, J.K., Cyktor, J.C., Fyne, E., Campellone, S., Mason, S.W., and Mellors, J.W. (2019). Blockade of the PD-1 axis alone is not sufficient to activate HIV-1 virion production from CD4+ T cells of individuals on suppressive ART. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0211112"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1038\/s41467-019-08798-7","article-title":"PD-1 blockade potentiates HIV latency reversal ex vivo in CD4(+) T cells from ART-suppressed individuals","volume":"10","author":"Fromentin","year":"2019","journal-title":"Nat. Commun."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/12\/1104\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:38:22Z","timestamp":1760189902000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/12\/1104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,11,28]]},"references-count":168,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["v11121104"],"URL":"https:\/\/doi.org\/10.3390\/v11121104","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,11,28]]}}}