Ait-Ammar, Amina; Université Libre de Bruxelles - ULB
Kula, Anna; Malopolska Centre of Biotechnology
DARCIS, Gilles ; Centre Hospitalier Universitaire de Liège - CHU > Département de médecine interne > Service des maladies infectieuses - médecine interne
Verdikt, Roxane; Université Libre de Bruxelles - ULB
De wit, Stéphane; CHU Saint-Pierre
Gautier, Virginie; University College Dublin
Mallon, PWG; University College Dublin
Marcello, Alessandro; International Centre for Genetic Engineering and Biotechnology
Rohr, Olivier; Université de Strasbourg
Van Lint, Carine; Université Libre de Bruxelles - ULB
Language :
English
Title :
Current Status of Latency Reversing Agents Facing the Heterogeneity of HIV-1 Cellular and Tissue Reservoirs.
Abdel-Mohsen M., Chavez L., Tandon R., Chew G. M., Deng X., Danesh A., et al. (2016). Human galectin-9 is a potent mediator of HIV transcription and reactivation. PLoS Pathog. 12:e1005677. 10.1371/journal.ppat.1005677 27253379
Abdel-Mohsen M., Kuri-Cervantes L., Grau-Exposito J., Spivak A. M., Nell R. A., Tomescu C., et al. (2018). CD32 is expressed on cells with transcriptionally active HIV but does not enrich for HIV DNA in resting T cells. Sci. Transl. Med. 10:eaar6759. 10.1126/scitranslmed.aar6759 29669853
Abner E., Stoszko M., Zeng L., Chen H.-C., Izquierdo-Bouldstridge A., Konuma T., (2018). A new quinoline BRD4 inhibitor targets a distinct latent HIV-1 reservoir for reactivation from other ‘shock’ drugs. J. Virol. 92:e02056-17. 10.1128/JVI.02056-17 29343578
Adams M., Sharmeen L., Kimpton J., Romeo J. M., Garcia J. V., Peterlin B. M., et al. (1994). Cellular latency in human immunodeficiency virus-infected individuals with high CD4 levels can be detected by the presence of promoter-proximal transcripts. Proc. Natl. Acad. Sci. U.S.A. 91 3862–3866. 10.1073/pnas.91.9.3862 8171003
Ajamian L., Abel K., Rao S., Vyboh K., García-de-Gracia F., Soto-Rifo R., et al. (2015). HIV-1 recruits UPF1 but excludes UPF2 to promote nucleocytoplasmic export of the genomic RNA. Biomolecules 5 2808–2839. 10.3390/biom5042808 26492277
Almodóvar S., Del C., Colón M., Maldonado I. M., Villafañe R., Abreu S., et al. (2007). HIV-1 infection of monocytes is directly related to the success of HAART. Virology 369 35–46. 10.1016/j.virol.2007.07.010 17707072
Archin N. M., Keedy K. S., Espeseth A., Dang H., Hazuda D. J., Margolis D. M., (2009). Expression of latent human immunodeficiency type 1 is induced by novel and selective histone deacetylase inhibitors. AIDS 23 1799–1806. 10.1097/QAD.0b013e32832ec1dc 19590405
Archin N. M., Liberty A. L., Kashuba A. D., Choudhary S. K., Kuruc J. D., Crooks A. M., et al. (2012). Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487 482–485. 10.1038/nature11286 22837004
Avettand-Fenoel V., Hocqueloux L., Müller-Trutwin M., Prazuck T., Melard A., (2011). Greater diversity of HIV DNA variants in the rectum compared to variants in the blood in patients without HAART. J. Med. Virol. 83 1499–1507. 10.1002/jmv.22132 21739438
Banga R., Procopio F. A., Cavassini M., Perreau M., (2016a). In vitro reactivation of replication-competent and infectious HIV-1 by histone deacetylase inhibitors. J. Virol. 90 1858–1871. 10.1128/JVI.02359-15 26656693
Banga R., Procopio F. A., Noto A., Pollakis G., Cavassini M., Ohmiti K., (2016b). PD-1(+) and follicular helper T cells are responsible for persistent HIV-1 transcription in treated aviremic individuals. Nat. Med. 22 754–761. 10.1038/nm.4113 27239760
Banga R., Procopio F. A., Ruggiero A., Noto A., Ohmiti K., Cavassini M., et al. (2018). Blood CXCR3+ CD4 T cells are enriched in inducible replication competent HIV in aviremic antiretroviral therapy-treated individuals. Front. Immunol. 9:144. 10.3389/fimmu.2018.00144 29459864
Bartholomeeusen K., Xiang Y., Fujinaga K., Peterlin B. M., (2012). 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. J. Biol. Chem. 287 36609–36616. 10.1074/jbc.M112.410746 22952229
Barton K., Hiener B., Winckelmann A., Rasmussen T. A., Shao W., Byth K., (2016). Broad activation of latent HIV-1 in vivo. Nat. Commun. 7:12731. 10.1038/ncomms12731 27605062
Battivelli E., Dahabieh M. S., Abdel-Mohsen M., Svensson J. P., Tojal Da Silva I., Cohn L. B., (2018). Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4+ T cells. eLife 7:e34655. 10.7554/eLife.34655 29714165
Baxter A. E., Niessl J., Fromentin R., Richard J., Porichis F., Charlebois R., (2016). Single-cell characterization of viral translation-competent reservoirs in HIV-infected individuals. Cell Host Microbe 20 368–380. 10.1016/j.chom.2016.07.015 27545045
Behrens N. E., Wertheimer A., Klotz S. A., Ahmad N., (2018). Reduction in terminally differentiated T cells in virologically controlled HIV-infected aging patients on long-term antiretroviral therapy. PLoS One 13:e0199101. 10.1371/journal.pone.0199101 29897981
Beliakova-Bethell N., Hezareh M., Wong J. K., Strain M. C., Lewinski M. K., Richman D. D., (2017). Relative efficacy of T cell stimuli as inducers of productive HIV-1 replication in latently infected CD4 lymphocytes from patients on suppressive cART. Virology 508 127–133. 10.1016/j.virol.2017.05.008 28527342
Berg S. L., Stone J., Xiao J. J., Chan K. K., Nuchtern J., Dauser R., et al. (2004). Plasma and cerebrospinal fluid pharmacokinetics of depsipeptide (FR901228) in nonhuman primates. Cancer Chemother. Pharmacol. 54 85–88. 10.1007/s00280-004-0766-5 15042312
Blazkova J., Murray D., Justement J. S., Funk E. K., Nelson A. K., Moir S., (2012). Paucity of HIV DNA methylation in latently infected, resting CD4+ T cells from infected individuals receiving antiretroviral therapy. J. Virol. 86 5390–5392. 10.1128/JVI.00040-12 22345448
Blazkova J., Trejbalova K., Gondois-Rey F., Halfon P., Philibert P., Guiguen A., et al. (2009). CpG methylation controls reactivation of HIV from latency. PLoS Pathog. 5:e1000554. 10.1371/journal.ppat.1000554 19696893
Boehm D., Jeng M., Camus G., Gramatica A., Schwarzer R., Johnson J. R., et al. (2017). SMYD2-mediated histone methylation contributes to HIV-1 latency. Cell Host Microbe 21 569–579.e6. 10.1016/j.chom.2017.04.011 28494238
Bosque A., Nilson K. A., Macedo A. B., Spivak A. M., Archin N. M., Van Wagoner R. M., et al. (2017). Benzotriazoles reactivate latent HIV-1 through inactivation of STAT5 SUMOylation. Cell Rep. 18 1324–1334. 10.1016/j.celrep.2017.01.022 28147284
Bouchat S., Delacourt N., Kula A., Darcis G., Van Driessche B., Corazza F., et al. (2016). Sequential treatment with 5-aza-2’-deoxycytidine and deacetylase inhibitors reactivates HIV-1. EMBO Mol. Med. 8 117–138. 10.15252/emmm.201505557 26681773
Bouchat S., Gatot J.-S., Kabeya K., Cardona C., Colin L., Herbein G., et al. (2012). Histone methyltransferase inhibitors induce HIV-1 recovery in resting CD4(+) T cells from HIV-1-infected HAART-treated patients. AIDS 26 1473–1482. 10.1097/QAD.0b013e32835535f5 22555163
Bradley T., Ferrari G., Haynes B. F., Margolis D. M., Browne E. P., (2018). Single-cell analysis of quiescent HIV infection reveals host transcriptional profiles that regulate proviral latency. Cell Rep. 25 107–117.e3. 10.1016/j.celrep.2018.09.020 30282021
Bruner K. M., Murray A. J., Pollack R. A., Soliman M. G., Laskey S. B., Capoferri A. A., (2016). Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat. Med. 22 1043–1049. 10.1038/nm.4156 27500724
Bruner K. M., Wang Z., Simonetti F. R., Bender A. M., Kwon K. J., Sengupta S., et al. (2019). A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature 566 120–125. 10.1038/s41586-019-0898-8 30700913
Budhiraja S., Famiglietti M., Bosque A., Planelles V., Rice A. P., (2013). Cyclin T1 and CDK9 T-loop phosphorylation are downregulated during establishment of HIV-1 latency in primary resting memory CD4+ T cells. J. Virol. 87 1211–1220. 10.1128/JVI.02413-12 23152527
Burnett J. C., Miller-Jensen K., Shah P. S., Arkin A. P., Schaffer D. V., (2009). Control of stochastic gene expression by host factors at the HIV promoter. PLoS Pathog. 5:e1000260. 10.1371/journal.ppat.1000260 19132086
Buzón M. J., Codoñer F. M., Frost S. D. W., Pou C., Puertas M. C., Massanella M., et al. (2011). Deep molecular characterization of HIV-1 dynamics under suppressive HAART. PLoS Pathog. 7:e1002314. 10.1371/journal.ppat.1002314 22046128
Buzon M. J., Sun H., Li C., Shaw A., Seiss K., Ouyang Z., (2014). HIV-1 persistence in CD4+ T cells with stem cell-like properties. Nat. Med. 20 139–142. 10.1038/nm.3445 24412925
Canaud G., Dejucq-Rainsford N., Avettand-Fenoël V., Viard J.-P., Anglicheau D., Bienaimé F., et al. (2014). The kidney as a reservoir for HIV-1 after renal transplantation. J. Am. Soc. Nephrol. 25 407–419. 10.1681/ASN.2013050564 24309185
Canestri A., Lescure F.-X., Jaureguiberry S., Moulignier A., Amiel C., Marcelin A. G., (2010). Discordance between cerebral spinal fluid and plasma HIV replication in patients with neurological symptoms who are receiving suppressive antiretroviral therapy. Clin. Infect. Dis. 50 773–778. 10.1086/650538 20100092
Cantero-Pérez J., Grau-Expósito J., Serra-Peinado C., Rosero D. A., Luque-Ballesteros L., Astorga-Gamaza A., et al. (2019). Resident memory T cells are a cellular reservoir for HIV in the cervical mucosa. Nat. Commun. 10:4739. 10.1038/s41467-019-12732-2 31628331
Cao W., Jamieson B. D., Hultin L. E., Hultin P. M., Effros R. B., Detels R., (2009). Premature aging of T cells is associated with faster HIV-1 disease progression. J. Acquir. Immune Defic. Syndr. 50 137–147. 10.1097/QAI.0b013e3181926c28 19131896
Caragounis E.-C., Gisslén M., Lindh M., Nordborg C., Westergren S., Hagberg L., et al. (2008). Comparison of HIV-1 pol and env sequences of blood, CSF, brain and spleen isolates collected ante-mortem and post-mortem. Acta Neurol. Scand. 117 108–116. 10.1111/j.1600-0404.2007.00914.x 18184346
Cary D. C., Peterlin B. M., (2018). Procyanidin trimer C1 reactivates latent HIV as a triple combination therapy with kansui and JQ1. PLoS One 13:e0208055. 10.1371/journal.pone.0208055 30475902
Casazza J. P., Betts M. R., Picker L. J., Koup R. A., (2001). Decay kinetics of human immunodeficiency virus-specific CD8+ T cells in peripheral blood after initiation of highly active antiretroviral therapy. J. Virol. 75 6508–6516. 10.1128/jvi.75.14.6508-6516.2001 11413318
Chang C. C., Naranbhai V., Stern J., Roche M., Dantanarayana A., Ke R., (2018). Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1. AIDS 32 2119–2128. 10.1097/QAD.0000000000001937 30005017
Chavez L., Calvanese V., Verdin E., (2015). HIV latency is established directly and early in both resting and activated primary CD4 T cells. PLoS Pathog. 11:e1004955. 10.1371/journal.ppat.1004955 26067822
Chávez L., Kauder S., Verdin E., (2011). In vivo, in vitro, and in silico analysis of methylation of the HIV-1 provirus. Methods 53 47–53. 10.1016/j.ymeth.2010.05.009 20670606
Chen H.-C., Martinez J. P., Zorita E., Meyerhans A., Filion G. J., (2017). Position effects influence HIV latency reversal. Nat. Struct. Mol. Biol. 24 47–54. 10.1038/nsmb.3328 27870832
Chen H.-C., Zorita E., Filion G. J., (2018). Using barcoded HIV ensembles (B-HIVE) for single provirus transcriptomics. Curr. Protoc. Mol. Biol. 122:e56. 10.1002/cpmb.56 29851299
Cherrier T., Le Douce V., Eilebrecht S., Riclet R., Marban C., Dequiedt F., et al. (2013). CTIP2 is a negative regulator of P-TEFb. Proc. Natl. Acad. Sci. U.S.A. 110 12655–12660. 10.1073/pnas.1220136110 23852730
Chomont N., El-Far M., Ancuta P., Trautmann L., Procopio F. A., Yassine-Diab B., (2009). HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat. Med. 15 893–900. 10.1038/nm.1972 19543283
Chun T.-W., Carruth L., Finzi D., Shen X., DiGiuseppe J. A., Taylor H., (1997). Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection. Nature 387 183–188. 10.1038/387183a0 9144289
Chun T.-W., Nickle D. C., Justement J. S., Meyers J. H., Roby G., Hallahan C. W., et al. (2008). Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J. Infect. Dis. 197 714–720. 10.1086/527324 18260759
Cicala C., Martinelli E., McNally J. P., Goode D. J., Gopaul R., Hiatt J., et al. (2009). The integrin alpha4beta7 forms a complex with cell-surface CD4 and defines a T-cell subset that is highly susceptible to infection by HIV-1. Proc. Natl. Acad. Sci. U.S.A. 106 20877–20882. 10.1073/pnas.0911796106 19933330
Clutton G., Xu Y., Baldoni P. L., Mollan K. R., Kirchherr J., Newhard W., (2016). The differential short- and long-term effects of HIV-1 latency-reversing agents on T cell function. Sci. Rep. 6:30749.
Clutton G. T., Jones R. B., (2018). Diverse impacts of HIV latency-reversing agents on CD8+ T-cell function: implications for HIV cure. Front. Immunol. 9:1452. 10.3389/fimmu.2018.01452 29988382
Cockerham L. R., Siliciano J. D., Sinclair E., O’Doherty U., Palmer S., Yukl S. A., et al. (2014). CD4+ and CD8+ T cell activation are associated with HIV DNA in resting CD4+ T cells. PLoS One 9:e110731. 10.1371/journal.pone.0110731 25340755
Colin L., Van Lint C., (2009). Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies. Retrovirology 6:111. 10.1186/1742-4690-6-111 19961595
Connick E., Mattila T., Folkvord J. M., Schlichtemeier R., Meditz A. L., Ray M. G., et al. (2007). CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue. J. Immunol. 178 6975–6983. 10.4049/jimmunol.178.11.6975 17513747
Contreras X., Barboric M., Lenasi T., Peterlin B. M., (2007). HMBA releases P-TEFb from HEXIM1 and 7SK snRNA via PI3K/Akt and activates HIV transcription. PLoS Pathog. 3:e146. 10.1371/journal.ppat.0030146 17937499
Coombs R. W., Lockhart D., Ross S. O., Deutsch L., Dragavon J., Diem K., et al. (2006). Lower genitourinary tract sources of seminal HIV. J. Acquir. Immune Defic. Syndr. 41 430–438. 10.1097/01.qai.0000209895.82255.08 16652050
Coombs R. W., Reichelderfer P. S., Landay A. L., (2003). Recent observations on HIV type-1 infection in the genital tract of men and women. AIDS 17 455–480. 10.1097/00002030-200303070-00001 12598766
Core L. J., Lis J. T., (2008). Transcription regulation through promoter-proximal pausing of RNA polymerase II. Science 319 1791–1792. 10.1126/science.1150843 18369138
Costiniuk C. T., Jenabian M.-A., (2014). The lungs as anatomical reservoirs of HIV infection. Rev. Med. Virol. 24 35–54. 10.1002/rmv.1772 24151040
Couturier J., Suliburk J. W., Brown J. M., Luke D. J., Agarwal N., Yu X., et al. (2015). Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS 29 667–674. 10.1097/QAD.0000000000000599 25849830
Cribbs S. K., Lennox J., Caliendo A. M., Brown L. A., Guidot D. M., (2015). Healthy HIV-1-infected individuals on highly active antiretroviral therapy harbor HIV-1 in their alveolar macrophages. AIDS Res. Hum. Retroviruses 31 64–70. 10.1089/AID.2014.0133 25134819
Darcis G., Berkhout B., Pasternak A. O., (2019). The quest for cellular markers of HIV reservoirs: any color you like. Front. Immunol. 10:2251. 10.3389/fimmu.2019.02251 31616425
Darcis G., Bouchat S., Kula A., Van Driessche B., Delacourt N., Vanhulle C., (2017). Reactivation capacity by latency-reversing agents ex vivo correlates with the size of the HIV-1 reservoir. AIDS 31 181–189. 10.1097/QAD.0000000000001290 27755105
Darcis G., Coombs R. W., Van Lint C., (2016). Exploring the anatomical HIV reservoirs: role of the testicular tissue. AIDS 30 2891–2893. 10.1097/qad.0000000000001281 27824627
Darcis G., Kula A., Bouchat S., Fujinaga K., Corazza F., Ait-Ammar A., (2015). An in-depth comparison of latency-reversing agent combinations in various in vitro and ex vivo HIV-1 latency models identified bryostatin-1+JQ1 and ingenol-B+JQ1 to potently reactivate viral gene expression. PLoS Pathog. 11:e1005063. 10.1371/journal.ppat.1005063 26225566
Das B., Dobrowolski C., Luttge B., Valadkhan S., Chomont N., Johnston R., (2018). Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir. Proc. Natl. Acad. Sci. U.S.A. 115 E7795–E7804. 10.1073/pnas.1803468115 30061382
Davey R. T., Bhat N., Yoder C., Chun T.-W., Metcalf J. A., Dewar R., (1999). HIV-1 and T cell dynamics after interruption of highly active antiretroviral therapy (HAART) in patients with a history of sustained viral suppression. Proc. Natl. Acad. Sci. U.S.A. 96 15109–15114. 10.1073/pnas.96.26.15109 10611346
De Scheerder M.-A., Vrancken B., Dellicour S., Schlub T., Lee E., Shao W., (2019). HIV rebound is predominantly fueled by genetically identical viral expansions from diverse reservoirs. Cell Host Microbe 26 347–358.e7. 10.1016/j.chom.2019.08.003 31471273
Debyser Z., Vansant G., Bruggemans A., Janssens J., Christ F., (2018). Insight in HIV integration site selection provides a block-and-lock strategy for a functional cure of HIV infection. Viruses 11:E12. 10.3390/v11010012 30587760
DeChristopher B. A., Loy B. A., Marsden M. D., Schrier A. J., Zack J. A., Wender P. A., (2012). Designed, synthetically accessible bryostatin analogues potently induce activation of latent HIV reservoirs in vitro. Nat. Chem. 4 705–710. 10.1038/nchem.1395 22914190
Deleage C., Wietgrefe S. W., Del Prete G., Morcock D. R., Hao X. P., Piatak M., et al. (2016). Defining HIV and SIV reservoirs in lymphoid tissues. Pathog. Immun. 1 68–106. 27430032
Della Chiara G., Crotti A., Liboi E., Giacca M., Poli G., Lusic M., (2011). Negative regulation of HIV-1 transcription by a heterodimeric NF-κB1/p50 and C-terminally truncated STAT5 complex. J. Mol. Biol. 410 933–943. 10.1016/j.jmb.2011.03.044 21763497
Delwart E. L., Mullins J. I., Gupta P., Learn G. H., Holodniy M., Katzenstein D., et al. (1998). Human immunodeficiency virus type 1 populations in blood and semen. J. Virol. 72 617–623. 10.1128/jvi.72.1.617-623.1998 9420266
Deng K., Pertea M., Rongvaux A., Wang L., Durand C. M., Ghiaur G., et al. (2015). Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517 381–385. 10.1038/nature14053 25561180
Descours B., Petitjean G., López-Zaragoza J.-L., Bruel T., Raffel R., Psomas C., et al. (2017). CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses. Nature 543 564–567. 10.1038/nature21710 28297712
Desimio M. G., Giuliani E., Doria M., (2017). The histone deacetylase inhibitor SAHA simultaneously reactivates HIV-1 from latency and up-regulates NKG2D ligands sensitizing for natural killer cell cytotoxicity. Virology 510 9–21. 10.1016/j.virol.2017.06.033 28689087
Desimio M. G., Giuliani E., Ferraro A. S., Adorno G., Doria M., (2018). In vitro exposure to prostratin but not bryostatin-1 improves natural killer cell functions including killing of CD4+ T cells harboring reactivated human immunodeficiency virus. Front. Immunol. 9:1514. 10.3389/fimmu.2018.01514 30008723
Diem K., Nickle D. C., Motoshige A., Fox A., Ross S., Mullins J. I., et al. (2008). Male genital tract compartmentalization of human immunodeficiency virus type 1 (HIV). AIDS Res. Hum. Retroviruses 24 561–571. 10.1089/aid.2007.0115 18426336
Ding D., Qu X., Li L., Zhou X., Liu S., Lin S., et al. (2013). Involvement of histone methyltransferase GLP in HIV-1 latency through catalysis of H3K9 dimethylation. Virology 440 182–189. 10.1016/j.virol.2013.02.022 23541084
Doyon G., Zerbato J., Mellors J. W., Sluis-Cremer N., (2013). Disulfiram reactivates latent HIV-1 expression through depletion of the phosphatase and tensin homolog. AIDS 27 F7–F11. 10.1097/QAD.0b013e3283570620 22739395
du Chéné I., Basyuk E., Lin Y.-L., Triboulet R., Knezevich A., Chable-Bessia C., (2007). Suv39H1 and HP1gamma are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J. 26 424–435. 10.1038/sj.emboj.7601517 17245432
Eilebrecht S., Le Douce V., Riclet R., Targat B., Hallay H., Van Driessche B., et al. (2014). HMGA1 recruits CTIP2-repressed P-TEFb to the HIV-1 and cellular target promoters. Nucleic Acids Res. 42 4962–4971. 10.1093/nar/gku168 24623795
Einkauf K. B., Lee G. Q., Gao C., Sharaf R., Sun X., Hua S., (2019). Intact HIV-1 proviruses accumulate at distinct chromosomal positions during prolonged antiretroviral therapy. J. Clin. Invest. 129 988–998. 10.1172/JCI124291 30688658
Eisele E., Siliciano R. F., (2012). Redefining the viral reservoirs that prevent HIV-1 eradication. Immunity 37 377–388. 10.1016/j.immuni.2012.08.010 22999944
Elliott J. H., McMahon J. H., Chang C. C., Lee S. A., Hartogensis W., Bumpus N., (2015). Short-term administration of disulfiram for reversal of latent HIV infection: a phase 2 dose-escalation study. Lancet HIV 2 e520–e529. 10.1016/S2352-3018(15)00226-X 26614966
Elliott J. H., Wightman F., Solomon A., Ghneim K., Ahlers J., Cameron M. J., (2014). Activation of HIV transcription with short-course vorinostat in HIV-infected patients on suppressive antiretroviral therapy. PLoS Pathog. 10:e1004473. 10.1371/journal.ppat.1004473 25393648
Evans V. A., van der Sluis R. M., Solomon A., Dantanarayana A., McNeil C., Garsia R., et al. (2018). Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency. AIDS 32 1491–1497. 10.1097/QAD.0000000000001849 29746296
Evering T. H., Mehandru S., Racz P., Tenner-Racz K., Poles M. A., Figueroa A., et al. (2012). Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection. PLoS Pathog. 8:e1002506. 10.1371/journal.ppat.1002506 22319447
Fletcher C. V., Staskus K., Wietgrefe S. W., Rothenberger M., Reilly C., Chipman J. G., et al. (2014). Persistent HIV-1 replication is associated with lower antiretroviral drug concentrations in lymphatic tissues. Proc. Natl. Acad. Sci. U.S.A. 111 2307–2312. 10.1073/pnas.1318249111 24469825
Forlani G., Tosi G., Turrini F., Poli G., Vicenzi E., Accolla R. S., (2017). Tripartite motif-containing protein 22 interacts with class II transactivator and orchestrates its recruitment in nuclear bodies containing TRIM19/PML and cyclin T1. Front. Immunol. 8:564. 10.3389/fimmu.2017.00564 28555140
Forouzanfar F., Ali S., Wallet C., Rovere M. D., Ducloy C., Mekdad H. E., et al. (2019). HIV-1 Vpr mediates the depletion of the cellular repressor CTIP2 to counteract viral gene silencing. Sci. Rep. 9:13154. 10.1038/s41598-019-48689-x 31511615
Friedman J., Cho W.-K., Chu C. K., Keedy K. S., Archin N. M., Margolis D. M., et al. (2011). Epigenetic silencing of HIV-1 by the histone H3 lysine 27 methyltransferase enhancer of zeste 2▽. J. Virol. 85 9078–9089. 10.1128/JVI.00836-11 21715480
Fromentin R., Bakeman W., Lawani M. B., Khoury G., Hartogensis W., DaFonseca S., et al. (2016). CD4+ T cells expressing PD-1, TIGIT and LAG-3 contribute to HIV persistence during ART. PLoS Pathog. 12:e1005761. 10.1371/journal.ppat.1005761 27415008
Ganor Y., Real F., Sennepin A., Dutertre C.-A., Prevedel L., Xu L., et al. (2019). HIV-1 reservoirs in urethral macrophages of patients under suppressive antiretroviral therapy. Nat. Microbiol. 4 633–644. 10.1038/s41564-018-0335-z 30718846
Garrido C., Spivak A. M., Soriano-Sarabia N., Checkley M. A., Barker E., Karn J., et al. (2016). HIV latency-reversing agents have diverse effects on natural killer cell function. Front. Immunol. 7:356. 10.3389/fimmu.2016.00356 27708642
Gattinoni L., Lugli E., Ji Y., Pos Z., Paulos C. M., Quigley M. F., (2011). A human memory T cell subset with stem cell-like properties. Nat. Med. 17 1290–1297. 10.1038/nm.2446 21926977
Geng G., Liu B., Chen C., Wu K., Liu J., Zhang Y., (2016). Development of an attenuated tat protein as a highly-effective agent to specifically activate HIV-1 latency. Mol. Ther. 24 1528–1537. 10.1038/mt.2016.117 27434587
Gianella S., Kosakovsky Pond S. L., Oliveira M. F., Scheffler K., Strain M. C., De la Torre A., (2016). Compartmentalized HIV rebound in the central nervous system after interruption of antiretroviral therapy. Virus Evol. 2:vew020. 10.1093/ve/vew020 27774305
Gibellini D., Borderi M., De Crignis E., Cicola R., Cimatti L., Vitone F., et al. (2008). HIV-1 DNA load analysis in peripheral blood lymphocytes and monocytes from naïve and HAART-treated individuals. J. Infect. 56 219–225. 10.1016/j.jinf.2008.01.001 18276011
Gohda J., Suzuki K., Liu K., Xie X., Takeuchi H., Inoue J.-I., et al. (2018). BI-2536 and BI-6727, dual Polo-like kinase/bromodomain inhibitors, effectively reactivate latent HIV-1. Sci. Rep. 8:3521. 10.1038/s41598-018-21942-5 29476067
Golumbeanu M., Cristinelli S., Rato S., Munoz M., Cavassini M., Beerenwinkel N., et al. (2018). Single-cell RNA-seq reveals transcriptional heterogeneity in latent and reactivated HIV-infected cells. Cell Rep. 23 942–950. 10.1016/j.celrep.2018.03.102 29694901
Gosselin A., Monteiro P., Chomont N., Diaz-Griffero F., Said E. A., Fonseca S., et al. (2010). Peripheral blood CCR4+CCR6+ and CXCR3+CCR6+CD4+ T cells are highly permissive to HIV-1 infection. J. Immunol. 184 1604–1616. 10.4049/jimmunol.0903058 20042588
Gosselin A., Wiche Salinas T. R., Planas D., Wacleche V. S., Zhang Y., Fromentin R., (2017). HIV persists in CCR6+CD4+ T cells from colon and blood during antiretroviral therapy. AIDS 31 35–48. 10.1097/qad.0000000000001309 27835617
Gras G., Kaul M., (2010). Molecular mechanisms of neuroinvasion by monocytes-macrophages in HIV-1 infection. Retrovirology 7:30. 10.1186/1742-4690-7-30 20374632
Grau-Expósito J., Luque-Ballesteros L., Navarro J., Curran A., Burgos J., Ribera E., (2019). Latency reversal agents affect differently the latent reservoir present in distinct CD4+ T subpopulations. PLoS Pathog. 15:e1007991. 10.1371/journal.ppat.1007991 31425551
Gray C. M., Lawrence J., Schapiro J. M., Altman J. D., Winters M. A., (1999). Frequency of class I HLA-restricted anti-HIV CD8+ T cells in individuals receiving highly active antiretroviral therapy (HAART). J. Immunol. 162 1780–1788. 9973442
Greger I. H., Demarchi F., Giacca M., Proudfoot N. J., (1998). Transcriptional interference perturbs the binding of Sp1 to the HIV-1 promoter. Nucleic Acids Res. 26 1294–1301. 10.1093/nar/26.5.1294 9469840
Guihot A., Marcelin A.-G., Massiani M.-A., Samri A., Soulié C., Autran B., et al. (2018). Drastic decrease of the HIV reservoir in a patient treated with nivolumab for lung cancer. Ann. Oncol. 29 517–518. 10.1093/annonc/mdx696
Gunst J. D., Kjær K., Olesen R., Rasmussen T. A., Østergaard L., Denton P. W., et al. (2019). Fimepinostat, a novel dual inhibitor of HDAC and PI3K, effectively reverses HIV-1 latency ex vivo without T cell activation. J. Virus Erad. 5 133–137.
Hakre S., Chavez L., Shirakawa K., Verdin E., (2012). HIV latency: experimental systems and molecular models. FEMS Microbiol. Rev. 36 706–716. 10.1111/j.1574-6976.2012.00335.x 22372374
Han Y., Lassen K., Monie D., Sedaghat A. R., Shimoji S., Liu X., et al. (2004). Resting CD4+ T cells from human immunodeficiency virus type 1 (HIV-1)-infected individuals carry integrated HIV-1 genomes within actively transcribed host genes. J. Virol. 78 6122–6133. 10.1128/jvi.78.12.6122-6133.2004 15163705
Han Y., Lin Y. B., An W., Xu J., Yang H.-C., O’Connell K., et al. (2008). Orientation-dependent regulation of integrated HIV-1 expression by host gene transcriptional readthrough. Cell Host Microbe 4 134–146. 10.1016/j.chom.2008.06.008 18692773
Hattori S., Matsuda K., Tsuchiya K., Gatanaga H., Oka S., Yoshimura K., (2018). Combination of a latency-reversing agent with a Smac mimetic minimizes secondary HIV-1 infection in vitro. Front. Microbiol. 9:2022. 10.3389/fmicb.2018.02022 30283406
Hayashi T., Jean M., Huang H., Simpson S., Santoso N. G., Zhu J., (2017). Screening of an FDA-approved compound library identifies levosimendan as a novel anti-HIV-1 agent that inhibits viral transcription. Antiviral Res. 146 76–85. 10.1016/j.antiviral.2017.08.013 28842263
Heesters B. A., Lindqvist M., Vagefi P. A., Scully E. P., Schildberg F. A., Altfeld M., (2015). Follicular dendritic cells retain infectious HIV in cycling endosomes. PLoS Pathog. 11:e1005285. 10.1371/journal.ppat.1005285 26623655
Hiener B., Horsburgh B. A., Eden J.-S., Barton K., Schlub T. E., Lee E., (2017). Identification of genetically intact HIV-1 proviruses in specific CD4+ T cells from effectively treated participants. Cell Rep. 21 813–822. 10.1016/j.celrep.2017.09.081 29045846
Ho Y.-C., Shan L., Hosmane N. N., Wang J., Laskey S. B., Rosenbloom D. I. S., et al. (2013). Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155 540–551. 10.1016/j.cell.2013.09.020 24243014
Hogan L. E., Vasquez J., Hobbs K. S., Hanhauser E., Aguilar-Rodriguez B., Hussien R., (2018). Increased HIV-1 transcriptional activity and infectious burden in peripheral blood and gut-associated CD4+ T cells expressing CD30. PLoS Pathog. 14:e1006856. 10.1371/journal.ppat.1006856 29470552
Honeycutt J. B., Thayer W. O., Baker C. E., Ribeiro R. M., Lada S. M., Cao Y., et al. (2017). HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat. Med. 23 638–643. 10.1038/nm.4319 28414330
Houzet L., Pérez-Losada M., Matusali G., Deleage C., Dereuddre-Bosquet N., Satie A.-P., et al. (2018). Seminal simian immunodeficiency virus in chronically infected cynomolgus macaques is dominated by virus originating from multiple genital organs. J. Virol. 92:e00133-18. 10.1128/JVI.00133-18 29720516
Hu Z., Kuritzkes D. R., (2014). Altered viral fitness and drug susceptibility in HIV-1 carrying mutations that confer resistance to nonnucleoside reverse transcriptase and integrase strand transfer inhibitors. J. Virol. 88 9268–9276. 10.1128/JVI.00695-14 24899199
Huang H., Kong W., Jean M., Fiches G., Zhou D., Hayashi T., et al. (2019). A CRISPR/Cas9 screen identifies the histone demethylase MINA53 as a novel HIV-1 latency-promoting gene (LPG). Nucleic Acids Res. 47 7333–7347. 10.1093/nar/gkz493 31165872
Huang H., Liu S., Jean M., Simpson S., Huang H., Merkley M., (2017). A novel bromodomain inhibitor reverses HIV-1 latency through specific binding with BRD4 to promote tat and P-TEFb association. Front. Microbiol. 8:1035. 10.3389/fmicb.2017.01035 28638377
Huang J., Wang F., Argyris E., Chen K., Liang Z., Tian H., (2007). Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat. Med. 13 1241–1247. 10.1038/nm1639 17906637
Hurst J., Hoffmann M., Pace M., Williams J. P., Thornhill J., Hamlyn E., et al. (2015). Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nat. Commun. 6:8495. 10.1038/ncomms9495 26449164
Iglesias-Ussel M., Vandergeeten C., Marchionni L., Chomont N., Romerio F., (2013). High levels of CD2 expression identify HIV-1 latently infected resting memory CD4+ T cells in virally suppressed subjects. J. Virol. 87 9148–9158. 10.1128/JVI.01297-13 23760244
Imai K., Togami H., Okamoto T., (2010). Involvement of histone H3 lysine 9 (H3K9) methyltransferase G9a in the maintenance of HIV-1 latency and its reactivation by BIX01294. J. Biol. Chem. 285 16538–16545. 10.1074/jbc.M110.103531 20335163
Imamichi H., Degray G., Dewar R. L., Mannon P., Yao M., Chairez C., et al. (2011). Lack of compartmentalization of HIV-1 quasispecies between the gut and peripheral blood compartments. J. Infect. Dis. 204 309–314. 10.1093/infdis/jir259 21673043
Iversen A. K. N., Attermann J., Gerstoft J., Fugger L., Mullins J. I., Skinhøj P., (2004). Longitudinal and cross-sectional studies of HIV-1 RNA and DNA loads in blood and the female genital tract. Eur. J. Obstet. Gynecol. Reprod. Biol. 117 227–235. 10.1016/j.ejogrb.2004.05.016 15541862
Jadlowsky J. K., Wong J. Y., Graham A. C., Dobrowolski C., Devor R. L., Adams M. D., et al. (2014). Negative elongation factor is required for the maintenance of proviral latency but does not induce promoter-proximal pausing of RNA polymerase II on the HIV long terminal repeat. Mol. Cell Biol. 34 1911–1928. 10.1128/MCB.01013-13 24636995
Jean M. J., Hayashi T., Huang H., Brennan J., Simpson S., Purmal A., (2017). Curaxin CBL0100 blocks HIV-1 replication and reactivation through inhibition of viral transcriptional elongation. Front. Microbiol. 8:2007. 10.3389/fmicb.2017.02007 29089933
Jenabian M.-A., Costiniuk C. T., Mehraj V., Ghazawi F. M., Fromentin R., Brousseau J., et al. (2016). Immune tolerance properties of the testicular tissue as a viral sanctuary site in ART-treated HIV-infected adults. AIDS 30 2777–2786. 10.1097/qad.0000000000001282 27677162
Jiang G., Espeseth A., Hazuda D. J., Margolis D. M., (2007). c-Myc and Sp1 contribute to proviral latency by recruiting histone deacetylase 1 to the human immunodeficiency virus type 1 promoter. J. Virol. 81 10914–10923. 10.1128/jvi.01208-07 17670825
Jiang G., Mendes E. A., Kaiser P., Sankaran-Walters S., Tang Y., Weber M. G., (2014). Reactivation of HIV latency by a newly modified Ingenol derivative via protein kinase Cδ-NF-κB signaling. AIDS 28 1555–1566. 10.1097/qad.0000000000000289 24804860
Jiang G., Mendes E. A., Kaiser P., Wong D. P., Tang Y., Cai I., et al. (2015). Synergistic reactivation of latent HIV expression by Ingenol-3-angelate, PEP005, targeted NF-kB signaling in combination with JQ1 induced p-TEFb activation. PLoS Pathog. 11:e1005066. 10.1371/journal.ppat.1005066 26225771
Jiang G., Nguyen D., Archin N. M., Yukl S. A., Méndez-Lagares G., Tang Y., et al. (2018). HIV latency is reversed by ACSS2-driven histone crotonylation. J. Clin. Invest. 128 1190–1198. 10.1172/JCI98071 29457784
Jones R. B., Mueller S., O’Connor R., Rimpel K., Sloan D. D., Karel D., (2016). A subset of latency-reversing agents expose HIV-infected resting CD4+ T-cells to recognition by cytotoxic T-lymphocytes. PLoS Pathog. 12:e1005545. 10.1371/journal.ppat.1005545 27082643
Jones R. B., O’Connor R., Mueller S., Foley M., Szeto G. L., Karel D., (2014). Histone deacetylase inhibitors impair the elimination of HIV-infected cells by cytotoxic T-lymphocytes. PLoS Pathog. 10:e1004287. 10.1371/journal.ppat.1004287 25122219
Kaiser P., Joshi S. K., Kim P., Li P., Liu H., Rice A. P., (2017). Assays for precise quantification of total (including short) and elongated HIV-1 transcripts. J. Virol. Methods 242 1–8. 10.1016/j.jviromet.2016.12.017 28034670
Kandathil A. J., Sugawara S., Balagopal A., (2016). Are T cells the only HIV-1 reservoir? Retrovirology 13:86.
Kauder S. E., Bosque A., Lindqvist A., Planelles V., Verdin E., (2009). Epigenetic regulation of HIV-1 latency by cytosine methylation. PLoS Pathog. 5:e1000495. 10.1371/journal.ppat.1000495 19557157
Kessing C. F., Nixon C. C., Li C., Tsai P., Takata H., Mousseau G., (2017). In vivo suppression of HIV rebound by didehydro-cortistatin A, a ‘block-and-lock’ strategy for HIV-1 treatment. Cell Rep. 21 600–611. 10.1016/j.celrep.2017.09.080 29045830
Kim Y., Anderson J. L., Lewin S. R., (2018). Getting the “kill” into “shock and kill”: strategies to eliminate latent HIV. Cell Host Microbe 23 14–26. 10.1016/j.chom.2017.12.004 29324227
Klase Z., Kale P., Winograd R., Gupta M. V., Heydarian M., Berro R., et al. (2007). HIV-1 TAR element is processed by Dicer to yield a viral micro-RNA involved in chromatin remodeling of the viral LTR. BMC Mol. Biol. 8:63. 10.1186/1471-2199-8-63 17663774
Klein K., Nickel G., Nankya I., Kyeyune F., Demers K., Ndashimye E., et al. (2018). Higher sequence diversity in the vaginal tract than in blood at early HIV-1 infection. PLoS Pathog. 14:e1006754. 10.1371/journal.ppat.1006754 29346424
Kohler S. L., Pham M. N., Folkvord J. M., Arends T., Miller S. M., Miles B., et al. (2016). Germinal center T follicular helper cells are highly permissive to HIV-1 and alter their phenotype during virus replication. J. Immunol. 196 2711–2722. 10.4049/jimmunol.1502174 26873986
Kuai Q., Lu X., Qiao Z., Wang R., Wang Y., Ye S., (2018). Histone deacetylase inhibitor chidamide promotes reactivation of latent human immunodeficiency virus by introducing histone acetylation. J. Med. Virol. 90 1478–1485. 10.1002/jmv.25207 29704439
Kula A., Delacourt N., Bouchat S., Darcis G., Avettand-Fenoel V., Verdikt R., (2019). Heterogeneous HIV-1 reactivation patterns of disulfiram and combined disulfiram+romidepsin treatments. J. Acquir. Immune Defic. Syndr. 80 605–613. 10.1097/QAI.0000000000001958 30768485
Kula A., Gharu L., Marcello A., (2013). HIV-1 pre-mRNA commitment to Rev mediated export through PSF and matrin 3. Virology 435 329–340. 10.1016/j.virol.2012.10.032 23158102
Kula A., Guerra J., Knezevich A., Kleva D., Myers M. P., Marcello A., (2011). Characterization of the HIV-1 RNA associated proteome identifies matrin 3 as a nuclear cofactor of Rev function. Retrovirology 8:60. 10.1186/1742-4690-8-60 21771346
Kulkosky J., Culnan D. M., Roman J., Dornadula G., Schnell M., Boyd M. R., et al. (2001). Prostratin: activation of latent HIV-1 expression suggests a potential inductive adjuvant therapy for HAART. Blood 98 3006–3015. 10.1182/blood.v98.10.3006 11698284
Kulpa D. A., Talla A., Brehm J. H., Ribeiro S. P., Yuan S., Bebin-Blackwell A.-G., (2019). Differentiation into an effector memory phenotype potentiates HIV-l latency reversal in CD4+ T cells. J. Virol. 93:e00969-19. 10.1128/JVI.00969-19 31578289
Kumar A., Abbas W., Herbein G., (2014). HIV-1 latency in monocytes/macrophages. Viruses 6 1837–1860. 10.3390/v6041837 24759213
Laird G. M., Bullen C. K., Rosenbloom D. I. S., Martin A. R., Hill A. L., Durand C. M., et al. (2015). Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. J. Clin. Invest. 125 1901–1912. 10.1172/JCI80142 25822022
Lambotte O., Taoufik Y., de Goër M. G., Wallon C., Goujard C., Delfraissy J. F., (2000). Detection of infectious HIV in circulating monocytes from patients on prolonged highly active antiretroviral therapy. J. Acquir. Immune Defic. Syndr. 23 114–119. 10.1097/00126334-200002010-00002 10737425
Lassen K. G., Ramyar K. X., Bailey J. R., Zhou Y., Siliciano R. F., (2006). Nuclear retention of multiply spliced HIV-1 RNA in resting CD4+ T cells. PLoS Pathog. 2:e68. 10.1371/journal.ppat.0020068 16839202
Lavolé A., Guihot A., Veyri M., Lambotte O., Autran B., Cloarec N., et al. (2018). PD-1 blockade in HIV-infected patients with lung cancer: a new challenge or already a strategy? Ann. Oncol. 29 1065–1066. 10.1093/annonc/mdx817
Le Garff G., Samri A., Lambert-Niclot S., Even S., Lavolé A., Cadranel J., (2017). Transient HIV-specific T cells increase and inflammation in an HIV-infected patient treated with nivolumab. AIDS 31 1048–1051. 10.1097/qad.0000000000001429 28350581
Lenasi T., Contreras X., Peterlin B. M., (2008). Transcriptional interference antagonizes proviral gene expression to promote HIV latency. Cell Host Microbe 4 123–133. 10.1016/j.chom.2008.05.016 18692772
Lerner P., Guadalupe M., Donovan R., Hung J., Flamm J., Prindiville T., et al. (2011). The gut mucosal viral reservoir in HIV-infected patients is not the major source of rebound plasma viremia following interruption of highly active antiretroviral therapy. J. Virol. 85 4772–4782. 10.1128/jvi.02409-10 21345945
Leth S., Schleimann M. H., Nissen S. K., Højen J. F., Olesen R., Graversen M. E., (2016). Combined effect of Vacc-4x, recombinant human granulocyte macrophage colony-stimulating factor vaccination, and romidepsin on the HIV-1 reservoir (REDUC): a single-arm, phase 1B/2A trial. Lancet HIV 3 e463–e472. 10.1016/S2352-3018(16)30055-8 27658863
Lewis M. J., Frohnen P., Ibarrondo F. J., Reed D., Iyer V., Ng H. L., et al. (2013). HIV-1 Nef sequence and functional compartmentalization in the gut is not due to differential cytotoxic T lymphocyte selective pressure. PLoS One 8:e75620. 10.1371/journal.pone.0075620 24058696
Li H., Pauza C. D., (2011). HIV envelope-mediated, CCR5/α4β7-dependent killing of CD4-negative γδ T cells which are lost during progression to AIDS. Blood 118 5824–5831. 10.1182/blood-2011-05-356535 21926353
Li J., Chen C., Ma X., Geng G., Liu B., Zhang Y., et al. (2016). Long noncoding RNA NRON contributes to HIV-1 latency by specifically inducing tat protein degradation. Nat. Commun. 7:11730. 10.1038/ncomms11730 27291871
Li Z., Mbonye U., Feng Z., Wang X., Gao X., Karn J., et al. (2018). The KAT5-acetyl-histone4-Brd4 axis silences HIV-1 transcription and promotes viral latency. PLoS Pathog. 14:e1007012. 10.1371/journal.ppat.1007012 29684085
Liang T., Zhang X., Lai F., Lin J., Zhou C., Xu X., (2019). A novel bromodomain inhibitor, CPI-203, serves as an HIV-1 latency-reversing agent by activating positive transcription elongation factor b. Biochem. Pharmacol. 164 237–251. 10.1016/j.bcp.2019.04.005 30991051
López-Huertas M. R., Jiménez-Tormo L., Madrid-Elena N., Gutiérrez C., Rodríguez-Mora S., Coiras M., (2017). The CCR5-antagonist maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist bryostatin-1. Sci. Rep. 7:2385. 10.1038/s41598-017-02634-y 28539614
Lu P., Qu X., Shen Y., Jiang Z., Wang P., Zeng H., (2016). The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb. Sci. Rep. 6:24100. 10.1038/srep24100 27067814
Lu P., Shen Y., Yang H., Wang Y., Jiang Z., Yang X., et al. (2017). BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency. Sci. Rep. 7:16646. 10.1038/s41598-017-16816-1 29192216
Lusic M., Marcello A., Cereseto A., Giacca M., (2003). Regulation of HIV-1 gene expression by histone acetylation and factor recruitment at the LTR promoter. EMBO J. 22 6550–6561. 10.1093/emboj/cdg631 14657027
Madrid-Elena N., García-Bermejo M. L., Serrano-Villar S., Díaz-de Santiago A., Sastre B., Gutiérrez C., (2018). Maraviroc is associated with latent HIV-1 reactivation through NF-κB activation in resting CD4+ T cells from HIV-infected individuals on suppressive antiretroviral therapy. J. Virol. 92:e019 31-17.
Malim M. H., Cullen B. R., (1991). HIV-1 structural gene expression requires the binding of multiple Rev monomers to the viral RRE: implications for HIV-1 latency. Cell 65 241–248. 10.1016/0092-8674(91)90158-u 2015625
Marban C., Suzanne S., Dequiedt F., de Walque S., Redel L., Van Lint C., et al. (2007). Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J. 26 412–423. 10.1038/sj.emboj.7601516 17245431
Marcelin A.-G., Tubiana R., Lambert-Niclot S., Lefebvre G., Dominguez S., Bonmarchand M., et al. (2008). Detection of HIV-1 RNA in seminal plasma samples from treated patients with undetectable HIV-1 RNA in blood plasma. AIDS 22 1677–1679. 10.1097/QAD.0b013e32830abdc8 18670231
Marini B., Kertesz-Farkas A., Ali H., Lucic B., Lisek K., Manganaro L., et al. (2015). Nuclear architecture dictates HIV-1 integration site selection. Nature 521 227–231. 10.1038/nature14226 25731161
Martin G. E., Pace M., Thornhill J. P., Phetsouphanh C., Meyerowitz J., Gossez M., et al. (2018). CD32-expressing CD4 T cells are phenotypically diverse and can contain proviral HIV DNA. Front. Immunol. 9:928. 10.3389/fimmu.2018.00928 29780387
Massanella M., Bakeman W., Sithinamsuwan P., Fletcher J. L. K., Chomchey N., Tipsuk S., et al. (2019). Infrequent HIV infection of circulating monocytes during antiretroviral therapy. J. Virol. 94:e01174-19. 10.1128/JVI.01174-19 31597764
Mates J. M., de Silva S., Lustberg M., Van Deusen K., Baiocchi R. A., Wu L., et al. (2015). A novel histone deacetylase inhibitor, AR-42, reactivates HIV-1 from chronically and latently infected CD4+ T-cells. Retrovirology 7 1–5. 26855567
McGary C. S., Deleage C., Harper J., Micci L., Ribeiro S. P., Paganini S., et al. (2017). CTLA-4+PD-1- memory CD4+ T cells critically contribute to viral persistence in antiretroviral therapy-suppressed, SIV-infected rhesus macaques. Immunity 47 776–788.e5. 10.1016/j.immuni.2017.09.018 29045906
McNamara L. A., Onafuwa-Nuga A., Sebastian N. T., Riddell J., Bixby D., Collins K. L., (2013). CD133+ hematopoietic progenitor cells harbor HIV genomes in a subset of optimally treated people with long-term viral suppression. J. Infect. Dis. 207 1807–1816. 10.1093/infdis/jit118 23554378
Miller R. L., Ponte R., Jones B. R., Kinloch N. N., Omondi F. H., Jenabian M.-A., (2019). HIV diversity and genetic compartmentalization in blood and testes during suppressive antiretroviral therapy. J. Virol. 93:e00755-19. 10.1128/JVI.00755-19 31189714
Miyawaki T., Kasahara Y., Taga K., Yachie A., Taniguchi N., (1990). Differential expression of CD45RO (UCHL1) and its functional relevance in two subpopulations of circulating TCR-gamma/delta+ lymphocytes. J. Exp. Med. 171 1833–1838. 10.1084/jem.171.5.1833 2139700
Modai S., Farberov L., Herzig E., Isakov O., Hizi A., Shomron N., (2019). HIV-1 infection increases microRNAs that inhibit Dicer1, HRB and HIV-EP2, thereby reducing viral replication. PLoS One 14:e0211111. 10.1371/journal.pone.0211111 30682089
Mohammadi P., di Iulio J., Muñoz M., Martinez R., Bartha I., Cavassini M., (2014). Dynamics of HIV latency and reactivation in a primary CD4+ T cell model. PLoS Pathog. 10:e1004156. 10.1371/journal.ppat.1004156 24875931
Moron-Lopez S., Kim P., Søgaard O. S., Tolstrup M., Wong J. K., Yukl S. A., (2019). Characterization of the HIV-1 transcription profile after romidepsin administration in ART-suppressed individuals. AIDS 33 425–431. 10.1097/QAD.0000000000002083 30531314
Mousseau G., Aneja R., Clementz M. A., Mediouni S., Lima N. S., Haregot A., et al. (2019). Resistance to the tat inhibitor didehydro-cortistatin a is mediated by heightened basal HIV-1 transcription. mBio 10:e01750-18. 10.1128/mBio.01750-18 31266880
Nguyen K., Das B., Dobrowolski C., Karn J., (2017). Multiple histone lysine methyltransferases are required for the establishment and maintenance of HIV-1 latency. mBio 8:e00133-17. 10.1128/mBio.00133-17 28246360
Nguyen V. T., Kiss T., Michels A. A., Bensaude O., (2001). 7SK small nuclear RNA binds to and inhibits the activity of CDK9/cyclin T complexes. Nature 414 322–325. 10.1038/35104581 11713533
Nolan D. J., Rose R., Rodriguez P. H., Salemi M., Singer E. J., Lamers S. L., (2018). The spleen is an HIV-1 sanctuary during combined antiretroviral therapy. AIDS Res. Hum. Retroviruses 34 123–125. 10.1089/AID.2017.0254 29084441
Norton N. J., Mok H. P., Sharif F., Hirst J. C., Lever A. M. L., (2019). HIV silencing and inducibility are heterogeneous and are affected by factors intrinsic to the virus. mBio 10:e00188-19. 10.1128/mBio.00188-19 31239371
Novis C. L., Archin N. M., Buzon M. J., Verdin E., Round J. L., Lichterfeld M., (2013). Reactivation of latent HIV-1 in central memory CD4+ T cells through TLR-1/2 stimulation. Retrovirology 10:119. 10.1186/1742-4690-10-119 24156240
Offersen R., Nissen S. K., Rasmussen T. A., Østergaard L., Denton P. W., Søgaard O. S., et al. (2016). 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. J. Virol. 90 4441–4453. 10.1128/JVI.00222-16 26889036
Oliveira M. F., Chaillon A., Nakazawa M., Vargas M., Letendre S. L., Strain M. C., (2017). Early antiretroviral therapy is associated with lower HIV DNA molecular diversity and lower inflammation in cerebrospinal fluid but does not prevent the establishment of compartmentalized HIV DNA populations. PLoS Pathog. 13:e1006112. 10.1371/journal.ppat.1006112 28046096
Osuna C. E., Lim S.-Y., Kublin J. L., Apps R., Chen E., Mota T. M., et al. (2018). Evidence that CD32a does not mark the HIV-1 latent reservoir. Nature 561 E20–E28.
Pace M. J., Graf E. H., Agosto L. M., Mexas A. M., Male F., Brady T., et al. (2012). Directly infected resting CD4+T cells can produce HIV Gag without spreading infection in a model of HIV latency. PLoS Pathog. 8:e1002818. 10.1371/journal.ppat.1002818 22911005
Pache L., Dutra M. S., Spivak A. M., Marlett J. M., Murry J. P., Hwang Y., et al. (2015). BIRC2/cIAP1 is a negative regulator of HIV-1 transcription and can be targeted by Smac mimetics to promote reversal of viral latency. Cell Host Microbe 18 345–353. 10.1016/j.chom.2015.08.009 26355217
Palacios J. A., Pérez-Piñar T., Toro C., Sanz-Minguela B., Moreno V., Valencia E., et al. (2012). Long-term nonprogressor and elite controller patients who control viremia have a higher percentage of methylation in their HIV-1 proviral promoters than aviremic patients receiving highly active antiretroviral therapy. J. Virol. 86 13081–13084. 10.1128/JVI.01741-12 22973038
Pallikkuth S., Sharkey M., Babic D. Z., Gupta S., Stone G. W., Fischl M. A., et al. (2015). Peripheral T follicular helper cells are the major HIV reservoir within central memory CD4 T cells in peripheral blood from chronically HIV-infected individuals on combination antiretroviral therapy. J. Virol. 90 2718–2728. 10.1128/JVI.02883-15 26676775
Paranjpe S., Craigo J., Patterson B., Ding M., Barroso P., Harrison L., et al. (2002). Subcompartmentalization of HIV-1 quasispecies between seminal cells and seminal plasma indicates their origin in distinct genital tissues. AIDS Res. Hum. Retroviruses 18 1271–1280. 10.1089/088922202320886316 12487815
Pardons M., Baxter A. E., Massanella M., Pagliuzza A., Fromentin R., Dufour C., (2019). Single-cell characterization and quantification of translation-competent viral reservoirs in treated and untreated HIV infection. PLoS Pathog. 15:e1007619. 10.1371/journal.ppat.1007619 30811499
Passaes C. P. B., Bruel T., Decalf J., David A., Angin M., Monceaux V., (2017). Ultrasensitive HIV-1 p24 assay detects single infected cells and differences in reservoir induction by latency reversal agents. J. Virol. 91:e02296-16. 10.1128/JVI.02296-16 28077644
Penton P. K., Blackard J. T., (2014). Analysis of HIV quasispecies suggests compartmentalization in the liver. AIDS Res. Hum. Retroviruses 30 394–402. 10.1089/AID.2013.0146 24074301
Perreau M., Savoye A.-L., De Crignis E., Corpataux J.-M., Cubas R., Haddad E. K., (2013). Follicular helper T cells serve as the major CD4 T cell compartment for HIV-1 infection, replication, and production. J. Exp. Med. 210 143–156. 10.1084/jem.20121932 23254284
Piantadosi A., Freije C. A., Gosmann C., Ye S., Park D., Schaffner S. F., et al. (2019). Metagenomic sequencing of HIV-1 in the blood and female genital tract reveals little quasispecies diversity during acute infection. J. Virol. 93:e00804-18. 10.1128/JVI.00804-18 30381486
Pillai S. K., Good B., Pond S. K., Wong J. K., Strain M. C., Richman D. D., et al. (2005). Semen-specific genetic characteristics of human immunodeficiency virus type 1 env. J. Virol. 79 1734–1742. 10.1128/jvi.79.3.1734-1742.2005 15650198
Pomerantz R. J., Trono D., Feinberg M. B., Baltimore D., (1990). Cells nonproductively infected with HIV-1 exhibit an aberrant pattern of viral RNA expression: a molecular model for latency. Cell 61 1271–1276. 10.1016/0092-8674(90)90691-7 2364429
Pulliam L., Gascon R., Stubblebine M., McGuire D., McGrath M. S., (1997). Unique monocyte subset in patients with AIDS dementia. Lancet 349 692–695. 10.1016/s0140-6736(96)10178-1 9078201
Quivy V., Adam E., Collette Y., Demonte D., Chariot A., Vanhulle C., et al. (2002). Synergistic activation of human immunodeficiency virus type 1 promoter activity by NF-kappaB and inhibitors of deacetylases: potential perspectives for the development of therapeutic strategies. J. Virol. 76 11091–11103. 10.1128/jvi.76.21.11091-11103.2002 12368351
Ramakrishnan R., Dow E. C., Rice A. P., (2009). Characterization of Cdk9 T-loop phosphorylation in resting and activated CD4(+) T lymphocytes. J. Leukoc. Biol. 86 1345–1350. 10.1189/jlb.0509309 19741158
Ramakrishnan R., Liu H., Rice A. P., (2015). Short communication: SAHA (vorinostat) induces CDK9 Thr-186 (T-loop) phosphorylation in resting CD4+ T cells: implications for reactivation of latent HIV. AIDS Res. Hum. Retroviruses 31 137–141. 10.1089/AID.2013.0288 24528253
Rao S., Amorim R., Niu M., Temzi A., Mouland A. J., (2018). The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level. Retrovirology 15:42. 10.1186/s12977-018-0425-2 29954456
Rasmussen T. A., Schmeltz Søgaard O., Brinkmann C., Wightman F., Lewin S. R., Melchjorsen J., (2013). Comparison of HDAC inhibitors in clinical development: effect on HIV production in latently infected cells and T-cell activation. Hum. Vaccin. Immunother. 9 993–1001. 10.4161/hv.23800 23370291
Rasmussen T. A., Tolstrup M., Brinkmann C. R., Olesen R., Erikstrup C., Solomon A., (2014). Panobinostat, a histone deacetylase inhibitor, for latent-virus reactivation in HIV-infected patients on suppressive antiretroviral therapy: a phase 1/2, single group, clinical trial. Lancet HIV 1 e13–e21. 10.1016/S2352-3018(14)70014-1 26423811
Rasmussen T. A., Tolstrup M., Møller H. J., Brinkmann C. R., Olesen R., Erikstrup C., (2015). Activation of latent human immunodeficiency virus by the histone deacetylase inhibitor panobinostat: a pilot study to assess effects on the central nervous system. Open Forum Infect. Dis. 2:ofv037. 10.1093/ofid/ofv037 26034779
Reuse S., Calao M., Kabeya K., Guiguen A., Gatot J.-S., Quivy V., et al. (2009). Synergistic activation of HIV-1 expression by deacetylase inhibitors and prostratin: implications for treatment of latent infection. PLoS One 4:e6093. 10.1371/journal.pone.0006093 19564922
Riou C., Yassine-Diab B., Van grevenynghe J., Somogyi R., Greller L. D., Gagnon D., (2007). Convergence of TCR and cytokine signaling leads to FOXO3a phosphorylation and drives the survival of CD4+ central memory T cells. J. Exp. Med. 204 79–91. 10.1084/jem.20061681 17190839
Rochat M. A., Schlaepfer E., Speck R. F., (2017). Promising role of toll-like receptor 8 agonist in concert with prostratin for activation of silent HIV. J. Virol. 91:e02084-16. 10.1128/JVI.02084-16 27928016
Rohr O., Lecestre D., Chasserot-Golaz S., Marban C., Avram D., Aunis D., et al. (2003). Recruitment of tat to heterochromatin protein HP1 via interaction with CTIP2 inhibits human immunodeficiency virus type 1 replication in microglial cells. J. Virol. 77 5415–5427. 10.1128/jvi.77.9.5415-5427.2003 12692243
Rothenberger M. K., Keele B. F., Wietgrefe S. W., Fletcher C. V., Beilman G. J., Chipman J. G., (2015). Large number of rebounding/founder HIV variants emerge from multifocal infection in lymphatic tissues after treatment interruption. Proc. Natl. Acad. Sci. U.S.A. 112 E1126–E1134. 10.1073/pnas.1414926112 25713386
Rozera G., Abbate I., Vlassi C., Giombini E., Lionetti R., Selleri M., et al. (2014). Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers. Clin. Microbiol. Infect. 20 157–166. 10.1111/1469-0691.12367 24134524
Saayman S., Ackley A., Turner A.-M. W., Famiglietti M., Bosque A., Clemson M., et al. (2014). An HIV-encoded antisense long noncoding RNA epigenetically regulates viral transcription. Mol. Ther. 22 1164–1175. 10.1038/mt.2014.29 24576854
Sadowski I., Hashemi F. B., (2019). Strategies to eradicate HIV from infected patients: elimination of latent provirus reservoirs. Cell. Mol. Life Sci. 76 3583–3600. 10.1007/s00018-019-03156-8 31129856
Salantes D. B., Zheng Y., Mampe F., Srivastava T., Beg S., Lai J., et al. (2018). HIV-1 latent reservoir size and diversity are stable following brief treatment interruption. J. Clin. Invest. 128 3102–3115. 10.1172/JCI120194 29911997
Sarracino A., Gharu L., Kula A., Pasternak A. O., Avettand-Fenoel V., Rouzioux C., et al. (2018). Posttranscriptional regulation of HIV-1 gene expression during replication and reactivation from latency by nuclear matrix protein MATR3. mBio 9:e02158-18. 10.1128/mBio.02158-18 30425153
Schlaepfer E., Speck R. F., (2011). TLR8 activates HIV from latently infected cells of myeloid-monocytic origin directly via the MAPK pathway and from latently infected CD4+ T cells indirectly via TNF-α. J. Immunol. 186 4314–4324. 10.4049/jimmunol.1003174
Schnell G., Price R. W., Swanstrom R., Spudich S., (2010). Compartmentalization and clonal amplification of HIV-1 variants in the cerebrospinal fluid during primary infection. J. Virol. 84 2395–2407. 10.1128/JVI.01863-09 20015984
Schröder A. R. W., Shinn P., Chen H., Berry C., Ecker J. R., Bushman F., (2002). HIV-1 integration in the human genome favors active genes and local hotspots. Cell 110 521–529. 10.1016/s0092-8674(02)00864-4 12202041
Schwartz C., Wallet C., De Rovere M., Van Assche J., Daoud F., Rohr O., (2019). Microglial cells: the main HIV-1 reservoir in the brain. Front. Cell. Infect. Microbiol. 9:362. 10.3389/fcimb.2019.00362 31709195
Scully E. P., Gandhi M., Johnston R., Hoh R., Lockhart A., Dobrowolski C., (2019). Sex-based differences in human immunodeficiency virus type 1 reservoir activity and residual immune activation. J. Infect. Dis. 219 1084–1094. 10.1093/infdis/jiy617 30371873
Scully E. P., Rutishauser R. L., Simoneau C. R., Delagrèverie H., Euler Z., Thanh C., et al. (2018). Inconsistent HIV reservoir dynamics and immune responses following anti-PD-1 therapy in cancer patients with HIV infection. Ann. Oncol. 29 2141–2142. 10.1093/annonc/mdy259
Sebastian N. T., Zaikos T. D., Terry V., Taschuk F., McNamara L. A., Onafuwa-Nuga A., et al. (2017). CD4 is expressed on a heterogeneous subset of hematopoietic progenitors, which persistently harbor CXCR4 and CCR5-tropic HIV proviral genomes in vivo. PLoS Pathog. 13:e1006509. 10.1371/journal.ppat.1006509 28732051
Sengupta S., Siliciano R. F., (2018). Targeting the latent reservoir for HIV-1. Immunity 48 872–895. 10.1016/j.immuni.2018.04.030 29768175
Serra-Peinado C., Grau-Expósito J., Luque-Ballesteros L., Astorga-Gamaza A., Navarro J., Gallego-Rodriguez J., et al. (2019). Expression of CD20 after viral reactivation renders HIV-reservoir cells susceptible to rituximab. Nat. Commun. 10:3705. 10.1038/s41467-019-11556-4 31420544
Sewald X., Ladinsky M. S., Uchil P. D., Beloor J., Pi R., Herrmann C., et al. (2015). Retroviruses use CD169-mediated trans-infection of permissive lymphocytes to establish infection. Science 350 563–567. 10.1126/science.aab2749 26429886
Shan L., Deng K., Shroff N. S., Durand C. M., Rabi S. A., Yang H.-C., (2012). Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36 491–501. 10.1016/j.immuni.2012.01.014 22406268
Shen R., Kappes J. C., Smythies L. E., Richter H. E., Novak L., Smith P. D., (2014). Vaginal myeloid dendritic cells transmit founder HIV-1. J. Virol. 88 7683–7688. 10.1128/JVI.00766-14 24741097
Sheth P. M., Kovacs C., Kemal K. S., Jones R. B., Raboud J. M., Pilon R., (2009). Persistent HIV RNA shedding in semen despite effective antiretroviral therapy. AIDS 23 2050–2054. 10.1097/QAD.0b013e3283303e04 19710596
Siddiqui S., Perez S., Gao Y., Doyle-Meyers L., Foley B. T., Li Q., et al. (2019). Persistent viral reservoirs in lymphoid tissues in SIV-infected rhesus macaques of Chinese-origin on suppressive antiretroviral therapy. Viruses 11:E105. 10.3390/v11020105 30691203
Singh P. K., Plumb M. R., Ferris A. L., Iben J. R., Wu X., (2015). LEDGF/p75 interacts with mRNA splicing factors and targets HIV-1 integration to highly spliced genes. Genes Dev. 29 2287–2297. 10.1101/gad.267609.115 26545813
Sivro A., Schuetz A., Sheward D., Joag V., Yegorov S., Liebenberg L. J., (2018). Integrin α4β7 expression on peripheral blood CD4+ T cells predicts HIV acquisition and disease progression outcomes. Sci. Transl. Med. 10:eaam6354. 10.1126/scitranslmed.aam6354 29367348
Smith B. A., Gartner S., Liu Y., Perelson A. S., Stilianakis N. I., Keele B. F., et al. (2001). Persistence of infectious HIV on follicular dendritic cells. J. Immunol. 166 690–696. 10.4049/jimmunol.166.1.690 11123354
Søgaard O. S., Graversen M. E., Leth S., Olesen R., Brinkmann C. R., Nissen S. K., (2015). The depsipeptide romidepsin reverses HIV-1 latency in vivo. PLoS Pathog. 11:e1005142. 10.1371/journal.ppat.1005142 26379282
Sonza S., Mutimer H. P., Oelrichs R., Jardine D., Harvey K., Dunne A., (2001). Monocytes harbour replication-competent, non-latent HIV-1 in patients on highly active antiretroviral therapy. AIDS 15 17–22. 10.1097/00002030-200101050-00005 11192864
Soriano-Sarabia N., Archin N. M., Bateson R., Dahl N. P., Crooks A. M., Kuruc J. D., et al. (2015). Peripheral Vγ9Vδ2 T cells are a novel reservoir of latent HIV infection. PLoS Pathog. 11:e1005201. 10.1371/journal.ppat.1005201 26473478
Spina C. A., Anderson J., Archin N. M., Bosque A., Chan J., Famiglietti M., (2013). An in-depth comparison of latent HIV-1 reactivation in multiple cell model systems and resting CD4+ T cells from aviremic patients. PLoS Pathog. 9:e1003834. 10.1371/journal.ppat.1003834 24385908
Spivak A. M., Andrade A., Eisele E., Hoh R., Bacchetti P., Bumpus N. N., (2014). A pilot study assessing the safety and latency-reversing activity of disulfiram in HIV-1-infected adults on antiretroviral therapy. Clin. Infect. Dis. 58 883–890. 10.1093/cid/cit813 24336828
Spivak A. M., Bosque A., Balch A. H., Smyth D., Martins L., Planelles V., (2015). Ex vivo bioactivity and HIV-1 latency reversal by ingenol dibenzoate and panobinostat in resting CD4(+) T cells from aviremic patients. Antimicrob. Agents Chemother. 59 5984–5991. 10.1128/AAC.01077-15 26169416
Spivak A. M., Planelles V., (2018). Novel latency reversal agents for HIV-1 cure. Annu. Rev. Med. 69 421–436. 10.1146/annurev-med-052716-031710 29099677
Sturdevant C. B., Joseph S. B., Schnell G., Price R. W., Swanstrom R., Spudich S., (2015). Compartmentalized replication of R5 T cell-tropic HIV-1 in the central nervous system early in the course of infection. PLoS Pathog. 11:e1004720. 10.1371/journal.ppat.1004720 25811757
Sung T.-L., Rice A. P., (2009). miR-198 inhibits HIV-1 gene expression and replication in monocytes and its mechanism of action appears to involve repression of cyclin T1. PLoS Pathog. 5:e1000263. 10.1371/journal.ppat.1000263 19148268
Suzuki K., Hattori S., Marks K., Ahlenstiel C., Maeda Y., Ishida T., (2013). Promoter targeting shRNA suppresses HIV-1 infection in vivo through transcriptional gene silencing. Mol. Ther. Nucleic Acids 2:e137. 10.1038/mtna.2013.64 24301868
Tapia G., Højen J. F., Ökvist M., Olesen R., Leth S., Nissen S. K., (2017). Sequential Vacc-4x and romidepsin during combination antiretroviral therapy (cART): immune responses to Vacc-4x regions on p24 and changes in HIV reservoirs. J. Infect. 75 555–571. 10.1016/j.jinf.2017.09.004 28917661
Taura M., Song E., Ho Y.-C., Iwasaki A., (2019). Apobec3A maintains HIV-1 latency through recruitment of epigenetic silencing machinery to the long terminal repeat. Proc. Natl. Acad. Sci. U.S.A. 116 2282–2289. 10.1073/pnas.1819386116 30670656
Tchasovnikarova I. A., Timms R. T., Douse C. H., Roberts R. C., Dougan G., Kingston R. E., et al. (2017). Hyperactivation of HUSH complex function by charcot-marie-tooth disease mutation in MORC2. Nat. Genet. 49 1035–1044. 10.1038/ng.3878 28581500
Tchasovnikarova I. A., Timms R. T., Matheson N. J., Wals K., Antrobus R., Göttgens B., (2015). Epigenetic silencing by the HUSH complex mediates position-effect variegation in human cells. Science 348 1481–1485. 10.1126/science.aaa7227 26022416
Telwatte S., Lee S., Somsouk M., Hatano H., Baker C., Kaiser P., et al. (2018). Gut and blood differ in constitutive blocks to HIV transcription, suggesting tissue-specific differences in the mechanisms that govern HIV latency. PLoS Pathog. 14:e1007357. 10.1371/journal.ppat.1007357 30440043
Thorlund K., Horwitz M. S., Fife B. T., Lester R., Cameron D. W., (2017). Landscape review of current HIV ‘kick and kill’ cure research - some kicking, not enough killing. BMC Infect. Dis. 17:595. 10.1186/s12879-017-2683-3 28851294
Thornhill J. P., Pace M., Martin G. E., Hoare J., Peake S., Herrera C., et al. (2019). CD32 expressing doublets in HIV-infected gut-associated lymphoid tissue are associated with a T follicular helper cell phenotype. Mucosal Immunol. 12 1212–1219. 10.1038/s41385-019-0180-2 31239514
Tran T.-A., de Goër de Herve M.-G., Hendel-Chavez H., Dembele B., Le Névot E., Abbed K., (2008). Resting regulatory CD4 T cells: a site of HIV persistence in patients on long-term effective antiretroviral therapy. PLoS One 3:e3305. 10.1371/journal.pone.0003305 18827929
Trejbalová K., Kováøová D., Blažková J., Machala L., Jilich D., Weber J., (2016). Development of 5′ LTR DNA methylation of latent HIV-1 provirus in cell line models and in long-term-infected individuals. Clin. Epigenetics 8:19. 10.1186/s13148-016-0185-6 26900410
Triboulet R., Mari B., Lin Y.-L., Chable-Bessia C., Bennasser Y., Lebrigand K., et al. (2007). Suppression of microRNA-silencing pathway by HIV-1 during virus replication. Science 315 1579–1582. 10.1126/science.1136319 17322031
Tripathy M. K., McManamy M. E. M., Burch B. D., Archin N. M., Margolis D. M., (2015). H3K27 demethylation at the proviral promoter sensitizes latent HIV to the effects of vorinostat in ex vivo cultures of resting CD4+ T cells. J. Virol. 89 8392–8405. 10.1128/JVI.00572-15 26041287
Tsai A., Irrinki A., Kaur J., Cihlar T., Kukolj G., Sloan D. D., et al. (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:e02166-16. 10.1128/JVI.02166-16 28179531
Turrini F., Marelli S., Kajaste-Rudnitski A., Lusic M., Van Lint C., Das A. T., et al. (2015). HIV-1 transcriptional silencing caused by TRIM22 inhibition of Sp1 binding to the viral promoter. Retrovirology 12:104. 10.1186/s12977-015-0230-0 26683615
Turrini F., Saliu F., Forlani G., Das A. T., Van Lint C., Accolla R. S., et al. (2019). Interferon-inducible TRIM22 contributes to maintenance of HIV-1 proviral latency in T cell lines. Virus Res. 269:197631. 10.1016/j.virusres.2019.05.009 31136823
Tyagi M., Karn J., (2007). CBF-1 promotes transcriptional silencing during the establishment of HIV-1 latency. EMBO J. 26 4985–4995. 10.1038/sj.emboj.7601928 18007589
Valcour V. G., Ananworanich J., Agsalda M., Sailasuta N., Chalermchai T., Schuetz A., et al. (2013). HIV DNA reservoir increases risk for cognitive disorders in cART-naïve patients. PLoS One 8:e70164. 10.1371/journal.pone.0070164 23936155
Valcour V. G., Shiramizu B. T., Shikuma C. M., (2010). HIV DNA in circulating monocytes as a mechanism to dementia and other HIV complications. J. Leukoc. Biol. 87 621–626. 10.1189/jlb.0809571 20130221
Valcour V. G., Shiramizu B. T., Sithinamsuwan P., Nidhinandana S., Ratto-Kim S., Ananworanich J., (2009). Asia research collaboration with the University of Hawaii 001 protocol team. HIV DNA and cognition in a thai longitudinal HAART initiation cohort: the SEARCH 001 cohort study. Neurology 72 992–998. 10.1212/01.wnl.0000344404.12759.83 19289739
van der Hoek L., Sol C. J., Maas J., Lukashov V. V., Kuiken C. L., Goudsmit J., (1998). Genetic differences between human immunodeficiency virus type 1 subpopulations in faeces and serum. J. Gen. Virol. 79(Pt 2), 259–267. 10.1099/0022-1317-79-2-259 9472610
Van Lint C., Bouchat S., Marcello A., (2013). HIV-1 transcription and latency: an update. Retrovirology 10:67. 10.1186/1742-4690-10-67 23803414
Van Lint C., Emiliani S., Ott M., Verdin E., (1996). Transcriptional activation and chromatin remodeling of the HIV-1 promoter in response to histone acetylation. EMBO J. 15 1112–1120. 10.1002/j.1460-2075.1996.tb00449.x 8605881
Venanzi Rullo E., Cannon L., Pinzone M. R., Ceccarelli M., Nunnari G., O’Doherty U., (2019). Genetic evidence that Naïve T cells can contribute significantly to the HIV intact reservoir: time to re-evaluate their role. Clin. Infect. Dis. 69 2236–2237. 10.1093/cid/ciz378 31063189
Verdin E., Paras P., Van Lint C., (1993). Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. EMBO J. 12 3249–3259. 10.1002/j.1460-2075.1993.tb05994.x 8344262
Vibholm L. K., Lorenzi J. C. C., Pai J. A., Cohen Y. Z., Oliveira T. Y., Barton J. P., (2019). Characterization of intact proviruses in blood and lymph node from HIV-infected individuals undergoing analytical treatment interruption. J. Virol. 93:e01920-18. 10.1128/JVI.01920-18 30700598
von Stockenstrom S., Odevall L., Lee E., Sinclair E., Bacchetti P., Killian M., et al. (2015). Longitudinal genetic characterization reveals that cell proliferation maintains a persistent HIV type 1 DNA pool during effective HIV therapy. J. Infect. Dis. 212 596–607. 10.1093/infdis/jiv092 25712966
Vranckx L. S., Demeulemeester J., Saleh S., Boll A., Vansant G., Schrijvers R., (2016). LEDGIN-mediated inhibition of integrase-LEDGF/p75 interaction reduces reactivation of residual latent HIV. EBioMedicine 8 248–264. 10.1016/j.ebiom.2016.04.039 27428435
Walker-Sperling V. E., Pohlmeyer C. W., Tarwater P. M., Blankson J. N., (2016). The effect of latency reversal agents on primary CD8+ T cells: implications for shock and kill strategies for human immunodeficiency virus eradication. EBioMedicine 8 217–229. 10.1016/j.ebiom.2016.04.019 27428432
Wan Z., Chen X., (2014). Triptolide inhibits human immunodeficiency virus type 1 replication by promoting proteasomal degradation of Tat protein. Retrovirology 11:88. 10.1186/s12977-014-0088-6 25323821
Weber S., Weiser B., Kemal K. S., Burger H., Ramirez C. M., Korn K., (2014). Epigenetic analysis of HIV-1 proviral genomes from infected individuals: predominance of unmethylated CpG’s. Virology 449 181–189. 10.1016/j.virol.2013.11.013 24418551
Wei P., Garber M. E., Fang S. M., Fischer W. H., Jones K. A., (1998). A novel CDK9-associated C-type cyclin interacts directly with HIV-1 Tat and mediates its high-affinity, loop-specific binding to TAR RNA. Cell 92 451–462. 10.1016/s0092-8674(00)80939-3 9491887
Weinberger L. S., Burnett J. C., Toettcher J. E., Arkin A. P., Schaffer D. V., (2005). Stochastic gene expression in a lentiviral positive-feedback loop: HIV-1 Tat fluctuations drive phenotypic diversity. Cell 122 169–182. 10.1016/j.cell.2005.06.006 16051143
Weng K.-F., Hung C.-T., Hsieh P.-T., Li M.-L., Chen G.-W., Kung Y. A., et al. (2014). A cytoplasmic RNA virus generates functional viral small RNAs and regulates viral IRES activity in mammalian cells. Nucleic Acids Res. 42 12789–12805. 10.1093/nar/gku952 25352551
Wightman F., Lu H. K., Solomon A. E., Saleh S., Harman A. N., Cunningham A. L., (2013). Entinostat is a histone deacetylase inhibitor selective for class 1 histone deacetylases and activates HIV production from latently infected primary T cells. AIDS 27 2853–2862. 10.1097/QAD.0000000000000067 24189584
Wightman F., Solomon A., Khoury G., Green J. A., Gray L., Gorry P. R., (2010). Both CD31(+) and CD31- naive CD4(+) T cells are persistent HIV type 1-infected reservoirs in individuals receiving antiretroviral therapy. J. Infect. Dis. 202 1738–1748. 10.1086/656721 20979453
Wightman F., Solomon A., Kumar S. S., Urriola N., Gallagher K., Hiener B., et al. (2015). Effect of ipilimumab on the HIV reservoir in an HIV-infected individual with metastatic melanoma. AIDS 29 504–506. 10.1097/qad.0000000000000562 25628259
Williams D. W., Veenstra M., Gaskill P. J., Morgello S., Calderon T. M., Berman J. W., (2014). Monocytes mediate HIV neuropathogenesis: mechanisms that contribute to HIV associated neurocognitive disorders. Curr. HIV Res. 12 85–96. 10.2174/1570162x12666140526114526 24862333
Williams S. A., Chen L.-F., Kwon H., Ruiz-Jarabo C. M., Verdin E., Greene W. C., (2006). NF-kappaB p50 promotes HIV latency through HDAC recruitment and repression of transcriptional initiation. EMBO J. 25 139–149. 10.1038/sj.emboj.7600900 16319923
Winckelmann A., Barton K., Hiener B., Schlub T. E., Shao W., Rasmussen T. A., (2017). Romidepsin-induced HIV-1 viremia during effective antiretroviral therapy contains identical viral sequences with few deleterious mutations. AIDS 31 771–779. 10.1097/QAD.0000000000001400 28272134
Winckelmann A., Morcilla V., Shao W., Schleimann M. H., Hojen J. F., Schlub T. E., et al. (2018). Genetic characterization of the HIV-1 reservoir after Vacc-4x and romidepsin therapy in HIV-1-infected individuals. AIDS 32 1793–1802. 10.1097/QAD.0000000000001861 29762162
Winston J. A., Bruggeman L. A., Ross M. D., Jacobson J., Ross L., D’Agati V. D., et al. (2001). Nephropathy and establishment of a renal reservoir of HIV type 1 during primary infection. N. Engl. J. Med. 344 1979–1984. 10.1056/nejm200106283442604 11430327
Xing S., Bullen C. K., Shroff N. S., Shan L., Yang H.-C., Manucci J. L., (2011). Disulfiram reactivates latent HIV-1 in a Bcl-2-transduced primary CD4+ T cell model without inducing global T cell activation. J. Virol. 85 6060–6064. 10.1128/JVI.02033-10 21471244
Yamaguchi Y., Takagi T., Wada T., Yano K., Furuya A., Sugimoto S., et al. (1999). NELF, a multisubunit complex containing RD, cooperates with DSIF to repress RNA polymerase II elongation. Cell 97 41–51. 10.1016/s0092-8674(00)80713-8 10199401
Yang W., Sun Z., Hua C., Wang Q., Xu W., Deng Q., et al. (2018). Chidamide, a histone deacetylase inhibitor-based anticancer drug, effectively reactivates latent HIV-1 provirus. Microbes Infect. 20 626–634. 10.1016/j.micinf.2017.10.003 29126877
Yang Z., Zhu Q., Luo K., Zhou Q., (2001). The 7SK small nuclear RNA inhibits the CDK9/cyclin T1 kinase to control transcription. Nature 414 317–322. 10.1038/35104575 11713532
Ylisastigui L., Archin N. M., Lehrman G., Bosch R. J., Margolis D. M., (2004). Coaxing HIV-1 from resting CD4 T cells: histone deacetylase inhibition allows latent viral expression. AIDS 18 1101–1108. 10.1097/00002030-200405210-00003 15166525
Yucha R. W., Hobbs K. S., Hanhauser E., Hogan L. E., Nieves W., Ozen M. O., (2017). High-throughput characterization of HIV-1 reservoir reactivation using a single-cell-in-droplet PCR assay. EBioMedicine 20 217–229. 10.1016/j.ebiom.2017.05.006 28529033
Yukl S. A., Kaiser P., Kim P., Telwatte S., Joshi S. K., Vu M., et al. (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:eaa9927. 10.1126/scitranslmed.aap9927 29491188
Yukl S. A., Shergill A. K., Ho T., Killian M., Girling V., Epling L., et al. (2013). The distribution of HIV DNA and RNA in cell subsets differs in gut and blood of HIV-positive patients on ART: implications for viral persistence. J. Infect. Dis. 208 1212–1220. 10.1093/infdis/jit308 23852128
Zaikos T. D., Terry V. H., Sebastian Kettinger N. T., Lubow J., Painter M. M., Virgilio M. C., (2018). Hematopoietic stem and progenitor cells are a distinct HIV reservoir that contributes to persistent viremia in suppressed patients. Cell Rep. 25 3759–3773.e9. 10.1016/j.celrep.2018.11.104 30590047
Zapata J. C., Campilongo F., Barclay R. A., DeMarino C., Iglesias-Ussel M. D., Kashanchi F., et al. (2017). The human immunodeficiency virus 1 ASP RNA promotes viral latency by recruiting the polycomb repressor complex 2 and promoting nucleosome assembly. Virology 506 34–44. 10.1016/j.virol.2017.03.002 28340355
Zerbato J. M., McMahon D. K., Sobolewski M. D., Mellors J. W., Sluis-Cremer N., (2019). Naïve CD4+ T cells harbor a large inducible reservoir of latent, replication-competent HIV-1. Clin. Infect. Dis. 69 1919–1925. 10.1093/cid/ciz108 30753360
Zhang Z., Nikolai B. C., Gates L. A., Jung S. Y., Siwak E. B., He B., (2017). Crosstalk between histone modifications indicates that inhibition of arginine methyltransferase CARM1 activity reverses HIV latency. Nucleic Acids Res. 45 9348–9360. 10.1093/nar/gkx550 28637181