CoChat
Sign Up
Cited by 163HIV Research and TreatmentVirus-based gene therapy researchHIV/AIDS drug development and treatment

Current status of latency reversing agents facing the heterogeneity of HIV-1 cellular and tissue reservoirs

Open access
Ait-Ammar, Amina, Kula, Anna, Darcis, Gilles, Verdikt, Roxane, De Wit, Stephane, Gautier, Virginie, Mallon, Patrick W. G., Marcello, Alessandro +2 more·2020·Frontiers in Microbiology
DOI 10.3389/fmicb.2019.03060PMC PMC6993040
Open this paper in CoChat — free accountOpen PDF

Abstract

One of the most explored therapeutic approach aiming at eradicating the HIV-1 reservoirs is the “shock and kill” strategy which is based on HIV-1 reactivation in latently-infected cells (“shock” phase), while maintaining ART in order to prevent spreading of the infection by the neosynthesized virus. This kind of strategy would allow the “kill” phase during which latently-infected cells would then die from viral cytopathic effects or from host cytolytic effector mechanisms following viral reactivation. Several latency reversing agents (LRAs) with distinct mechanistic classes have been characterized to reactivate HIV-1 viral gene expression. Some LRAs have been tested in terms of their potential to purge latent HIV-1 in vivo in clinical trials, showing that reversing HIV-1 latency is possible. However, LRAs alone have failed to reduce the size of the viral reservoirs. Together with the inability of the immune system to clear the LRA-activated reservoirs and the lack of specificity of these LRAs, the heterogeneity of the reservoirs largely contributes to the limited success of clinical trials using LRAs. Indeed, HIV-1 latency is established in numerous cell types that are characterized by distinct phenotypes and metabolic properties, and these are influenced by patient history. Hence, the silencing mechanisms of HIV-1 gene expression in these cellular and tissue reservoirs need to be better understood to rationally improve this cure strategy and hopefully reach clinical success.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3389/fmicb.2019.03060

Cites

4 of 4 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 299

  1. Abdel-Mohsen M. Chavez L. Tandon R. Chew G. M. Deng X. Danesh A. (2016). Human galectin-9 is a potent mediator of HIV transcription and reactivation. PLoS Pathog. 12: e1005677. 10.1371/journal.ppat.1005677 27253379 PMC4890776 · DOI
  2. Abdel-Mohsen M. Kuri-Cervantes L. Grau-Exposito J. Spivak A. M. Nell R. A. Tomescu C. (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 PMC6282755 · DOI
  3. 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 PMC5923069 · DOI
  4. Adams M. Sharmeen L. Kimpton J. Romeo J. M. Garcia J. V. Peterlin B. M. (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 PMC43682 · DOI
  5. Ajamian L. Abel K. Rao S. Vyboh K. García-de-Gracia F. Soto-Rifo R. (2015). HIV-1 recruits UPF1 but excludes UPF2 to promote nucleocytoplasmic export of the genomic RNA. Biomolecules 5 2808– 2839. 10.3390/biom5042808 26492277 PMC4693258 · DOI
  6. Almodóvar S. Del C. Colón M. Maldonado I. M. Villafañe R. Abreu S. (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 · DOI
  7. 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 PMC3809117 · DOI
  8. Archin N. M. Liberty A. L. Kashuba A. D. Choudhary S. K. Kuruc J. D. Crooks A. M. (2012). Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487 482– 485. 10.1038/nature11286 22837004 PMC3704185 · DOI
  9. 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 · DOI
  10. 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 PMC4733986 · DOI
  11. 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 · DOI
  12. Banga R. Procopio F. A. Ruggiero A. Noto A. Ohmiti K. Cavassini M. (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 PMC5807378 · DOI
  13. 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 PMC3476326 · DOI
  14. 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 PMC5025526 · DOI
  15. 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 PMC5973828 · DOI
  16. 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 PMC5025389 · DOI
  17. 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 PMC5999291 · DOI
  18. 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 PMC5654527 · DOI
  19. Berg S. L. Stone J. Xiao J. J. Chan K. K. Nuchtern J. Dauser R. (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 · DOI
  20. 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 PMC3347337 · DOI
  21. Blazkova J. Trejbalova K. Gondois-Rey F. Halfon P. Philibert P. Guiguen A. (2009). CpG methylation controls reactivation of HIV from latency. PLoS Pathog. 5: e1000554. 10.1371/journal.ppat.1000554 19696893 PMC2722084 · DOI
  22. Boehm D. Jeng M. Camus G. Gramatica A. Schwarzer R. Johnson J. R. (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 PMC5490666 · DOI
  23. Bosque A. Nilson K. A. Macedo A. B. Spivak A. M. Archin N. M. Van Wagoner R. M. (2017). Benzotriazoles reactivate latent HIV-1 through inactivation of STAT5 SUMOylation. Cell Rep. 18 1324– 1334. 10.1016/j.celrep.2017.01.022 28147284 PMC5461578 · DOI
  24. Bouchat S. Delacourt N. Kula A. Darcis G. Van Driessche B. Corazza F. (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 PMC4734845 · DOI
  25. Bouchat S. Gatot J.-S. Kabeya K. Cardona C. Colin L. Herbein G. (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 · DOI
  26. 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 PMC6258175 · DOI
  27. Bruner K. M. Wang Z. Simonetti F. R. Bender A. M. Kwon K. J. Sengupta S. (2019). A quantitative approach for measuring the reservoir of latent HIV-1 proviruses. Nature 566 120– 125. 10.1038/s41586-019-0898-8 30700913 PMC6447073 · DOI · Paper page
  28. 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 PMC3554045 · DOI
  29. 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 PMC2607019 · DOI
  30. Buzón M. J. Codoñer F. M. Frost S. D. W. Pou C. Puertas M. C. Massanella M. (2011). Deep molecular characterization of HIV-1 dynamics under suppressive HAART. PLoS Pathog. 7: e1002314. 10.1371/journal.ppat.1002314 22046128 PMC3203183 · DOI
  31. 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 PMC3959167 · DOI
  32. Canaud G. Dejucq-Rainsford N. Avettand-Fenoël V. Viard J.-P. Anglicheau D. Bienaimé F. (2014). The kidney as a reservoir for HIV-1 after renal transplantation. J. Am. Soc. Nephrol. 25 407– 419. 10.1681/ASN.2013050564 24309185 PMC3904571 · DOI
  33. 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 · DOI
  34. Cantero-Pérez J. Grau-Expósito J. Serra-Peinado C. Rosero D. A. Luque-Ballesteros L. Astorga-Gamaza A. (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 PMC6802119 · DOI
  35. 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 PMC2767229 · DOI
  36. Caragounis E.-C. Gisslén M. Lindh M. Nordborg C. Westergren S. Hagberg L. (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 · DOI
  37. 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 PMC6258234 · DOI
  38. 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 PMC114374 · DOI
  39. 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 PMC6173794 · DOI
  40. 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 PMC4466167 · DOI
  41. 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 PMC3566233 · DOI
  42. 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 · DOI
  43. 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 · DOI
  44. Cherrier T. Le Douce V. Eilebrecht S. Riclet R. Marban C. Dequiedt F. (2013). CTIP2 is a negative regulator of P-TEFb. Proc. Natl. Acad. Sci. U.S.A. 110 12655– 12660. 10.1073/pnas.1220136110 23852730 PMC3732990 · DOI
  45. 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 PMC2859814 · DOI
  46. Chun T.-W. Nickle D. C. Justement J. S. Meyers J. H. Roby G. Hallahan C. W. (2008). Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J. Infect. Dis. 197 714– 720. 10.1086/527324 18260759 · DOI
  47. Cicala C. Martinelli E. McNally J. P. Goode D. J. Gopaul R. Hiatt J. (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 PMC2780317 · DOI
  48. 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. PMC4969750 27480951
  49. 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 PMC6023971 · DOI
  50. Cockerham L. R. Siliciano J. D. Sinclair E. O’Doherty U. Palmer S. Yukl S. A. (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 PMC4207702 · DOI
  51. 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 PMC2797771 · DOI
  52. Connick E. Mattila T. Folkvord J. M. Schlichtemeier R. Meditz A. L. Ray M. G. (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 · DOI
  53. 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 PMC2014796 · DOI
  54. Coombs R. W. Lockhart D. Ross S. O. Deutsch L. Dragavon J. Diem K. (2006). Lower genitourinary tract sources of seminal HIV. J. Acquir. Immune Defic. Syndr. 41 430– 438. 10.1097/01.qai.0000209895.82255.08 16652050 · DOI
  55. 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 · DOI
  56. 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 PMC2833332 · DOI
  57. 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 · DOI
  58. Couturier J. Suliburk J. W. Brown J. M. Luke D. J. Agarwal N. Yu X. (2015). Human adipose tissue as a reservoir for memory CD4+ T cells and HIV. AIDS 29 667– 674. 10.1097/QAD.0000000000000599 25849830 PMC4389783 · DOI
  59. 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 PMC4287110 · DOI
  60. 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 PMC6763966 · DOI
  61. 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 · DOI
  62. 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 PMC5123776 · DOI
  63. 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 PMC4520688 · DOI
  64. 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 PMC6099847 · DOI
  65. 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 PMC24781 · DOI
  66. 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 PMC11021134 · DOI · Paper page
  67. 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 PMC6356730 · DOI
  68. 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 PMC3428736 · DOI
  69. Deleage C. Wietgrefe S. W. Del Prete G. Morcock D. R. Hao X. P. Piatak M. (2016). Defining HIV and SIV reservoirs in lymphoid tissues. Pathog. Immun. 1 68– 106. 27430032 PMC4943335
  70. 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 · DOI
  71. Delwart E. L. Mullins J. I. Gupta P. Learn G. H. Holodniy M. Katzenstein D. (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 PMC109415 · DOI
  72. Deng K. Pertea M. Rongvaux A. Wang L. Durand C. M. Ghiaur G. (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 PMC4406054 · DOI
  73. Descours B. Petitjean G. López-Zaragoza J.-L. Bruel T. Raffel R. Psomas C. (2017). CD32a is a marker of a CD4 T-cell HIV reservoir harbouring replication-competent proviruses. Nature 543 564– 567. 10.1038/nature21710 28297712 · DOI
  74. 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 · DOI
  75. 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 PMC6033996 · DOI
  76. Diem K. Nickle D. C. Motoshige A. Fox A. Ross S. Mullins J. I. (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 · DOI
  77. Ding D. Qu X. Li L. Zhou X. Liu S. Lin S. (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 · DOI
  78. 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 PMC1783455 · DOI
  79. Eilebrecht S. Le Douce V. Riclet R. Targat B. Hallay H. Van Driessche B. (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 PMC4005653 · DOI
  80. 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 PMC6391088 · DOI
  81. 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 PMC3963158 · DOI · Paper page
  82. 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 PMC5108570 · DOI · Paper page
  83. 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 PMC4231123 · DOI
  84. Evans V. A. van der Sluis R. M. Solomon A. Dantanarayana A. McNeil C. Garsia R. (2018). Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency. AIDS 32 1491– 1497. 10.1097/QAD.0000000000001849 29746296 PMC6026054 · DOI
  85. Evering T. H. Mehandru S. Racz P. Tenner-Racz K. Poles M. A. Figueroa A. (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 PMC3271083 · DOI
  86. Fletcher C. V. Staskus K. Wietgrefe S. W. Rothenberger M. Reilly C. Chipman J. G. (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 PMC3926074 · DOI
  87. 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 PMC5430032 · DOI
  88. Forouzanfar F. Ali S. Wallet C. Rovere M. D. Ducloy C. Mekdad H. E. (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 PMC6739472 · DOI
  89. Friedman J. Cho W.-K. Chu C. K. Keedy K. S. Archin N. M. Margolis D. M. (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 PMC3165831 · DOI
  90. Fromentin R. Bakeman W. Lawani M. B. Khoury G. Hartogensis W. DaFonseca S. (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 PMC4944956 · DOI
  91. Ganor Y. Real F. Sennepin A. Dutertre C.-A. Prevedel L. Xu L. (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 · DOI
  92. Garrido C. Spivak A. M. Soriano-Sarabia N. Checkley M. A. Barker E. Karn J. (2016). HIV latency-reversing agents have diverse effects on natural killer cell function. Front. Immunol. 7: 356. 10.3389/fimmu.2016.00356 27708642 PMC5030263 · DOI
  93. 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 PMC5113098 · DOI
  94. 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 PMC5072458 · DOI
  95. Gibellini D. Borderi M. De Crignis E. Cicola R. Cimatti L. Vitone F. (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 · DOI
  96. Gohda J. Suzuki K. Liu K. Xie X. Takeuchi H. Inoue J.-I. (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 PMC5824842 · DOI
  97. Golumbeanu M. Cristinelli S. Rato S. Munoz M. Cavassini M. Beerenwinkel N. (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 · DOI
  98. Gosselin A. Monteiro P. Chomont N. Diaz-Griffero F. Said E. A. Fonseca S. (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 PMC4321756 · DOI
  99. 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 PMC5131694 · DOI
  100. 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 PMC2864195 · DOI
  101. 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 PMC6715238 · DOI
  102. 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
  103. 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 PMC147389 · DOI
  104. Guihot A. Marcelin A.-G. Massiani M.-A. Samri A. Soulié C. Autran B. (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 29206889 · DOI
  105. Gunst J. D. Kjær K. Olesen R. Rasmussen T. A. Østergaard L. Denton P. W. (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. PMC6816120 31700655
  106. 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 PMC3563430 · DOI
  107. Han Y. Lassen K. Monie D. Sedaghat A. R. Shimoji S. Liu X. (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 PMC416493 · DOI
  108. Han Y. Lin Y. B. An W. Xu J. Yang H.-C. O’Connell K. (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 PMC2604135 · DOI
  109. 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 PMC6156138 · DOI
  110. 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 PMC5654649 · DOI
  111. 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 PMC4666623 · DOI
  112. 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 PMC5960642 · DOI · Paper page
  113. Ho Y.-C. Shan L. Hosmane N. N. Wang J. Laskey S. B. Rosenbloom D. I. S. (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 PMC3896327 · DOI · Paper page
  114. 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 PMC5823470 · DOI
  115. Honeycutt J. B. Thayer W. O. Baker C. E. Ribeiro R. M. Lada S. M. Cao Y. (2017). HIV persistence in tissue macrophages of humanized myeloid-only mice during antiretroviral therapy. Nat. Med. 23 638– 643. 10.1038/nm.4319 28414330 PMC5419854 · DOI
  116. Houzet L. Pérez-Losada M. Matusali G. Deleage C. Dereuddre-Bosquet N. Satie A.-P. (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 PMC6026730 · DOI
  117. 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 PMC4136249 · DOI
  118. Huang H. Kong W. Jean M. Fiches G. Zhou D. Hayashi T. (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 PMC6698651 · DOI
  119. 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 PMC5461361 · DOI
  120. 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 · DOI
  121. Hurst J. Hoffmann M. Pace M. Williams J. P. Thornhill J. Hamlyn E. (2015). Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nat. Commun. 6: 8495. 10.1038/ncomms9495 26449164 PMC4633715 · DOI
  122. 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 PMC3754042 · DOI
  123. 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 PMC2878073 · DOI
  124. Imamichi H. Degray G. Dewar R. L. Mannon P. Yao M. Chairez C. (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 PMC3114472 · DOI
  125. 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 · DOI
  126. Jadlowsky J. K. Wong J. Y. Graham A. C. Dobrowolski C. Devor R. L. Adams M. D. (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 PMC4019061 · DOI
  127. 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 PMC5651003 · DOI
  128. Jenabian M.-A. Costiniuk C. T. Mehraj V. Ghazawi F. M. Fromentin R. Brousseau J. (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 · DOI
  129. 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 PMC2045540 · DOI
  130. 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 PMC4922310 · DOI
  131. Jiang G. Mendes E. A. Kaiser P. Wong D. P. Tang Y. Cai I. (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 PMC4520526 · DOI
  132. Jiang G. Nguyen D. Archin N. M. Yukl S. A. Méndez-Lagares G. Tang Y. (2018). HIV latency is reversed by ACSS2-driven histone crotonylation. J. Clin. Invest. 128 1190– 1198. 10.1172/JCI98071 29457784 PMC5824862 · DOI
  133. 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 PMC4833318 · DOI
  134. 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 PMC4133386 · DOI
  135. 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 PMC5560404 · DOI
  136. Kandathil A. J. Sugawara S. Balagopal A. (2016). Are T cells the only HIV-1 reservoir? Retrovirology 13: 86. PMC5175311 27998285
  137. 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 PMC2695767 · DOI
  138. 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 PMC5653276 · DOI
  139. 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 PMC5990418 · DOI
  140. Klase Z. Kale P. Winograd R. Gupta M. V. Heydarian M. Berro R. (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 PMC1955452 · DOI
  141. Klein K. Nickel G. Nankya I. Kyeyune F. Demers K. Ndashimye E. (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 PMC5773221 · DOI
  142. Kohler S. L. Pham M. N. Folkvord J. M. Arends T. Miller S. M. Miles B. (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 PMC4779697 · DOI
  143. 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 · DOI
  144. 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 · DOI
  145. 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 · DOI
  146. 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 PMC3160904 · DOI
  147. Kulkosky J. Culnan D. M. Roman J. Dornadula G. Schnell M. Boyd M. R. (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 · DOI
  148. 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 PMC6880164 · DOI
  149. Kumar A. Abbas W. Herbein G. (2014). HIV-1 latency in monocytes/macrophages. Viruses 6 1837– 1860. 10.3390/v6041837 24759213 PMC4014723 · DOI
  150. Laird G. M. Bullen C. K. Rosenbloom D. I. S. Martin A. R. Hill A. L. Durand C. M. (2015). Ex vivo analysis identifies effective HIV-1 latency-reversing drug combinations. J. Clin. Invest. 125 1901– 1912. 10.1172/JCI80142 25822022 PMC4463209 · DOI
  151. 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 · DOI
  152. 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 PMC1487174 · DOI
  153. Lavolé A. Guihot A. Veyri M. Lambotte O. Autran B. Cloarec N. (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 29346600 · DOI
  154. 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 · DOI
  155. 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 PMC4217705 · DOI
  156. Lerner P. Guadalupe M. Donovan R. Hung J. Flamm J. Prindiville T. (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 PMC3126205 · DOI
  157. 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 · DOI
  158. Lewis M. J. Frohnen P. Ibarrondo F. J. Reed D. Iyer V. Ng H. L. (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 PMC3772905 · DOI
  159. 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 PMC3228498 · DOI
  160. Li J. Chen C. Ma X. Geng G. Liu B. Zhang Y. (2016). Long noncoding RNA NRON contributes to HIV-1 latency by specifically inducing tat protein degradation. Nat. Commun. 7: 11730. 10.1038/ncomms11730 27291871 PMC4909936 · DOI
  161. Li Z. Mbonye U. Feng Z. Wang X. Gao X. Karn J. (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 PMC5933813 · DOI
  162. 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 · DOI
  163. 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 PMC5443841 · DOI
  164. 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 PMC4828723 · DOI
  165. Lu P. Shen Y. Yang H. Wang Y. Jiang Z. Yang X. (2017). BET inhibitors RVX-208 and PFI-1 reactivate HIV-1 from latency. Sci. Rep. 7: 16646. 10.1038/s41598-017-16816-1 29192216 PMC5709369 · DOI
  166. 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 PMC291826 · DOI
  167. 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. PMC5899181 29444937
  168. 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 · DOI
  169. Marban C. Suzanne S. Dequiedt F. de Walque S. Redel L. Van Lint C. (2007). Recruitment of chromatin-modifying enzymes by CTIP2 promotes HIV-1 transcriptional silencing. EMBO J. 26 412– 423. 10.1038/sj.emboj.7601516 17245431 PMC1783449 · DOI
  170. Marcelin A.-G. Tubiana R. Lambert-Niclot S. Lefebvre G. Dominguez S. Bonmarchand M. (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 · DOI
  171. Marini B. Kertesz-Farkas A. Ali H. Lucic B. Lisek K. Manganaro L. (2015). Nuclear architecture dictates HIV-1 integration site selection. Nature 521 227– 231. 10.1038/nature14226 25731161 · DOI
  172. Martin G. E. Pace M. Thornhill J. P. Phetsouphanh C. Meyerowitz J. Gossez M. (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 PMC5946760 · DOI
  173. Massanella M. Bakeman W. Sithinamsuwan P. Fletcher J. L. K. Chomchey N. Tipsuk S. (2019). Infrequent HIV infection of circulating monocytes during antiretroviral therapy. J. Virol. 94: e01174-19. 10.1128/JVI.01174-19 31597764 PMC6912110 · DOI
  174. Mates J. M. de Silva S. Lustberg M. Van Deusen K. Baiocchi R. A. Wu L. (2015). A novel histone deacetylase inhibitor, AR-42, reactivates HIV-1 from chronically and latently infected CD4+ T-cells. Retrovirology 7 1– 5. 26855567 PMC4739806
  175. McGary C. S. Deleage C. Harper J. Micci L. Ribeiro S. P. Paganini S. (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 PMC5679306 · DOI
  176. 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 PMC3654754 · DOI
  177. 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 PMC6694813 · DOI
  178. 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 PMC2187907 · DOI
  179. 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 PMC6347224 · DOI
  180. 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 PMC4038609 · DOI
  181. 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 PMC6374101 · DOI
  182. Mousseau G. Aneja R. Clementz M. A. Mediouni S. Lima N. S. Haregot A. (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 PMC6606815 · DOI
  183. 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 PMC5347344 · DOI
  184. 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 · DOI
  185. 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 PMC5771542 · DOI
  186. 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 PMC6593397 · DOI
  187. 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 PMC3826617 · DOI
  188. Offersen R. Nissen S. K. Rasmussen T. A. Østergaard L. Denton P. W. Søgaard O. S. (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 PMC4836316 · DOI
  189. 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 PMC5266327 · DOI
  190. Osuna C. E. Lim S.-Y. Kublin J. L. Apps R. Chen E. Mota T. M. (2018). Evidence that CD32a does not mark the HIV-1 latent reservoir. Nature 561 E20– E28. 30232424 PMC6528470
  191. Pace M. J. Graf E. H. Agosto L. M. Mexas A. M. Male F. Brady T. (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 PMC3406090 · DOI · Paper page
  192. Pache L. Dutra M. S. Spivak A. M. Marlett J. M. Murry J. P. Hwang Y. (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 PMC4617541 · DOI
  193. Palacios J. A. Pérez-Piñar T. Toro C. Sanz-Minguela B. Moreno V. Valencia E. (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 PMC3497688 · DOI
  194. Pallikkuth S. Sharkey M. Babic D. Z. Gupta S. Stone G. W. Fischl M. A. (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 PMC4810658 · DOI
  195. Paranjpe S. Craigo J. Patterson B. Ding M. Barroso P. Harrison L. (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 · DOI
  196. 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 PMC6411230 · DOI
  197. 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 PMC5331803 · DOI
  198. 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 PMC5972776 · DOI
  199. 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 PMC3549706 · DOI
  200. Piantadosi A. Freije C. A. Gosmann C. Ye S. Park D. Schaffner S. F. (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 PMC6321908 · DOI

200 of 299 shown

Cited by

Sorted by citations

Authors
Ait-Ammar, A., Kula, A., Darcis, G., Verdikt, R., De Wit, S., Gautier, V., Mallon, P. W. G., Marcello, A., Rohr, O., & Van Lint, C.
Affiliations
  • Jagiellonian University (PL)
  • Centre Hospitalier Universitaire de Liège (BE)
  • Université Libre de Bruxelles (BE)
  • University College Dublin (IE)
  • International Centre for Genetic Engineering and Biotechnology (IT)
  • Université de Strasbourg (FR)
ORCID
Venue
Frontiers in Microbiology
Publisher
Frontiers Media SA
Published
2020-01-24
Volume
10
Pages
3060-3060
ISSN
1664-302X (ISSN-L)
DOI
10.3389/fmicb.2019.03060
PMC
PMC6993040
OpenAlex
W3000848632
Cited by
163
References
4
Citations by year
2026: 9 · 2025: 18 · 2024: 25 · 2023: 24 · 2022: 41 · 2021: 33 · 2020: 12 · 2019: 1
FWCI
4.46
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Microbiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • Lirias (submittedVersion, cc-by)
  • Jagiellonian University Repository (Jagiellonian University) (submittedVersion, other-oa)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • ORBi (University of Liège) (submittedVersion, other-oa)
  • univOAK (4 institutions : Université de Strasbourg, Université de Haute Alsace, INSA Strasbourg, Bibliothèque Nationale et Universitaire de Strasbourg) (submittedVersion, cc-by)
  • Lenus, The Irish Health Repository (Dr Steevens Hospital Library) (submittedVersion)
Funders
  • Health Research Board (ILP-POR-2017-084, ILP-POR-2019-081)
  • Les Amis des Instituts Pasteur à Bruxelles
  • European Commission (MSCA-RISE-2015, H2020‐MSCA‐RISE‐2015, 691119, HORIZON2020, H2020, H2020-MSCA, H2020 MSCA Rise)
  • Fonds De La Recherche Scientifique - FNRS
  • Koning Boudewijnstichting
  • Wallonie-Bruxelles International
  • Horizon 2020 Framework Programme (H2020-MSCA, H2020-MSCA-RISE, H2020-MSCA-RISE-2015, 691119, MSCA-RISE-2015)
Topics
  • Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS drug development and treatment
Keywords
latency-reversing agents, HIV-1 latency, HIV-1 reservoir, shock and kill strategy, viral reactivation, latent HIV-1, reservoir heterogeneity, HIV cure, antiretroviral therapy, clinical trials

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review