A broad drug arsenal to attack a strenuous latent HIV reservoir

Siliciano, 2015, The remarkable stability of the latent reservoir for HIV-1 in resting memory CD4 + T cells, J Infect Dis, 212, 1345, 10.1093/infdis/jiv219 Kessing, 2017, In vivo suppression of HIV rebound by Didehydro-Cortistatin A, a "Block-and-Lock" strategy for HIV-1 treatment, Cell Rep, 17, 600, 10.1016/j.celrep.2017.09.080 Deeks, 2012, HIV: shock and kill, Nature, 25, 439, 10.1038/487439a Kuhlmann, 2018, Chimeric antigen receptor T-cell approaches to HIV cure, Curr Opin HIV AIDS, 446, 10.1097/COH.0000000000000485 Gao, 2018, Advances in HIV-1 vaccine development, Viruses, 10, 10.3390/v10040167 Jones, 2016, HIV-specific CD8+T cells and HIV eradication, J Clin Invest, 126, 455, 10.1172/JCI80566 Kumar, 2018, Broadly neutralizing antibodies in HIV-1 treatment and prevention, Ther Adv Vaccines Immunother, 6, 61, 10.1177/2515135518800689 Ne, 2018, Transcription: insights from the HIV-1 promoter, Int Rev Cell Mol Biol, 335, 191, 10.1016/bs.ircmb.2017.07.011 De Crignis, 2017, The multifaceted contributions of chromatin to HIV-1 integration, transcription, and latency, Int Rev Cell Mol Biol, 328, 197, 10.1016/bs.ircmb.2016.08.006 Sarracino, 2017, The relevance of post-transcriptional mechanisms in HIV latency reversal, Curr Pharm Des, 23, 10.2174/1381612823666170803102355 Baxter, 2018, Beyond the replication-competent HIV reservoir: transcription and translation-competent reservoirs, Retrovirology, 15, 18, 10.1186/s12977-018-0392-7 Cary, 2016, Molecular mechanisms of HIV latency, J Clin Invest, 126, 448, 10.1172/JCI80565 Margolis, 2017, Proviral latency, persistent human immunodeficiency virus infection, and the development of latency reversing agents, J Infect Dis, 215, S111, 10.1093/infdis/jiw618 Khan, 2018, Epigenetic regulation of HIV-1 latency: focus on polycomb group (PcG) proteins, Clin Epigenet, 5, 14, 10.1186/s13148-018-0441-z Mbonye, 2017, The molecular basis for human immunodeficiency virus latency, Annu Rev Virol, 29, 261, 10.1146/annurev-virology-101416-041646 Boehm, 2017, Host methyltransferases and demethylases: potential new epigenetic targets for HIV cure strategies and beyond, AIDS Res Hum Retroviruse, 33, S8, 10.1089/aid.2017.0180 Jiang, 2018, HIV latency is reversed by ACSS2-driven histone crotonylation, J Clin Invest, 128, 1190, 10.1172/JCI98071 Rasmussen, 2018, Clinical interventions in HIV cure research, Adv Exp Med Biol, 1075, 285, 10.1007/978-981-13-0484-2_12 Archin, 2017, Interval dosing with the HDAC inhibitor vorinostat effectively reverses HIV latency, J Clin Invest, 1, 3126, 10.1172/JCI92684 Brinkmann, 2018, Treatment of HIV-infected individuals with the histone deacetylase inhibitor panobinostat results in increased numbers of regulatory T cells and limits ex vivo lipopolysaccharide-induced inflammatory responses, mSphere, 14 Spivak, 2017, Novel latency reversal agents for HIV-1 cure, Annu Rev Med, 69 Bolduc, 2017, Epigenetic metabolite acetate inhibits class I/II histone deacetylases, promotes histone acetylation, and increases HIV-1 integration in CD4+ T cells, J Virol, 91, 10.1128/JVI.01943-16 Dar, 2014, Screening for noise in gene expression identifies drug synergies, Science, 344, 1392, 10.1126/science.1250220 Wu, 2017, HDAC inhibition induces HIV-1 protein and enables immune-based clearance following latency reversal, JCI Insight, 2, 10.1172/jci.insight.92901 Albert, 2017, Combinations of isoform-targeted histone deacetylase inhibitors and bryostatin analogues display remarkable potency to activate latent HIV without global T-cell activation, Sci Rep, 7, 10.1038/s41598-017-07814-4 Zaikos, 2018, Class 1-Selective Histone Deacetylase (HDAC) inhibitors enhance HIV latency reversal while preserving the activity of HDAC isoforms necessary for maximal HIV gene expression, J Virol, 92, 10.1128/JVI.02110-17 Kobayashi, 2017, HDAC inhibitors containing a benzamide functional group and a Pyridyl cap are preferentially effective HIV-1 latency reversing agents in primary resting CD4+ T cells, J Gen Virol, 799, 10.1099/jgv.0.000716 Nguyen, 2017, Multiple histone lysine methyltransferases are required for the establishment and maintenance of HIV-1 latency, mBio, 28 Boehm, 2017, SMYD2-mediated histone methylation contributes to HIV-1 latency, Cell Host Microbe, 21, 569, 10.1016/j.chom.2017.04.011 Bouchat, 2016, Sequential treatment with 5-aza-2’-deoxycytidine and deacetylase inhibitors reactivates HIV-1, EMBO Mol Med, 8, 117, 10.15252/emmm.201505557 Conrad, 2017, The short isoform of BRD4 promotes HIV-1 latency by engaging repressive SWI/SNF chromatin-remodeling complexes, Mol Cell, 67, 1001, 10.1016/j.molcel.2017.07.025 Stoszko, 2015, Small molecule inhibitors of BAF; a promising family of compounds in HIV-1 latency reversal, BioMedicine, 27, 108 Marian, 2018, Small molecule targeting of specific BAF (mSWI/SNF) complexes for HIV latency reversal, Cell Chem Biol, 25, 1443, 10.1016/j.chembiol.2018.08.004 Megaridis, 2018, Fine-tuning of noise in gene expression with nucleosome remodeling, APL Bioeng, 2, 10.1063/1.5021183 Jiang, 2015, Targeting NF-κB signaling with protein kinase C agonists as an emerging strategy for combating HIV latency, AIDS Res Hum Retroviruses, 31, 4, 10.1089/aid.2014.0199 Bosque, 2017, Benzotriazoles reactivate latent HIV-1 through inactivation of STAT5 SUMOylation, Cell Rep, 18, 1324, 10.1016/j.celrep.2017.01.022 Pache, 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, 10.1016/j.chom.2015.08.009 Hattori, 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 Brogdon, 2016, In vitro effects of the small-molecule protein kinase C agonists on HIV latency reactivation, Sci Rep, 6, 10.1038/srep39032 Spivak, 2018, Synthetic ingenols maximize protein kinase C-induced HIV-1 latency reversal, Antimicrob Agents Chemother, 62, 10.1128/AAC.01361-18 Marsden, 2017, In vivo activation of latent HIV with a synthetic bryostatin analog effects both latent cell “kick” and “kill” in strategy for virus eradication, PLoS Pathog, 13, 10.1371/journal.ppat.1006575 Marsden, 2018, Characterization of designed, synthetically accessible bryostatin analog HIV latency reversing agents, Virology, 520, 83, 10.1016/j.virol.2018.05.006 Hashemi, 2018, Compounds producing an effective combinatorial regimen for disruption of HIV-1 latency, EMBO Mol Med, 10, 160, 10.15252/emmm.201708193 Matsuda, 2019, Benzolactam-related compounds promote apoptosis of HIV-infected human cells via protein kinase C-induced HIV latency reversal, J Biol Chem, 294, 116, 10.1074/jbc.RA118.005798 Gutiérrez, 2016, Bryostatin-1 for latent virus reactivation in HIV-infected patients on antiretroviral therapy, AIDS, 30, 1385, 10.1097/QAD.0000000000001064 Phetsouphanh, 2015, The role of PKC-θ in CD4+ T cells and HIV infection: to the nucleus and back again, Front Immunol, 30, 391 López-Huertas, 2017, The CCR5-antagonist maraviroc reverses HIV-1 latency in vitro alone or in combination with the PKC-agonist Bryostatin-1, Sci Rep, 7, 10.1038/s41598-017-02634-y Madrid-Elena, 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, 10.1128/JVI.01931-17 Macedo, 2018, Dual TLR2 and TLR7 agonists as HIV latency-reversing agents, JCI Insight, 3, 10.1172/jci.insight.122673 Vibholm, 2017, Short-course toll-like receptor 9 agonist treatment impacts innate immunity and plasma viremia in individuals with human immunodeficiency virus infection, Clin Infect Dis, 64, 1686, 10.1093/cid/cix201 Tsai, 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, 10.1128/JVI.02166-16 Lim, 2018, TLR7 agonists induce transient viremia and reduce the viral reservoir in SIV-infected rhesus macaques on antiretroviral therapy, Sci Transl Med, 10, 10.1126/scitranslmed.aao4521 Rochat, 2017, Promising role of toll-like receptor 8 agonist in concert with prostratin for activation of silent HIV, J Virol, 91, 10.1128/JVI.02084-16 Cheng, 2018, TLR3 agonist and CD40-targeting vaccination induces immune responses and reduces HIV-1 reservoirs, J Clin Invest, 128, 4387, 10.1172/JCI99005 Zeng, 2017, Resveratrol reactivates latent HIV through increasing histone acetylation and activating heat shock factor 1, J Agric Food Chem, 65, 4384, 10.1021/acs.jafc.7b00418 Yukl, 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, 10.1126/scitranslmed.aap9927 Jean, 2017, Identification of HIV-1 Tat-associated proteins contributing to HIV-1 transcription and latency, Viruses, 9, 67, 10.3390/v9040067 Khoury, 2018, HIV latency reversing agents act through Tat post translational modifications, Retrovirology, 15, 10.1186/s12977-018-0421-6 Mousseau, 2017, Role of host factors on the regulation of Tat-mediated HIV-1 transcription, Curr Pharm Des, 23, 4079, 10.2174/1381612823666170622104355 Abner, 2018, A new quinoline BRD4 inhibitor targets a distinct latent HIV-1 reservoir for reactivation from other “Shock” drugs, J Virol, 92, 10.1128/JVI.02056-17 Lu, 2016, The BET inhibitor OTX015 reactivates latent HIV-1 through P-TEFb, Sci Rep, 12 Huang, 2017, A novel bromodomain inhibitor reverses HIV-1 latency through specific binding with BRD4 to promote Tat and P-TEFb association, Front Microbiol, 7, 1035, 10.3389/fmicb.2017.01035 Darcis, 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, 10.1371/journal.ppat.1005063 Li, 2018, The KAT5-Acetyl-Histone4-Brd4 axis silences HIV-1 transcription and promotes viral latency, PLoS Pathog, 14, 10.1371/journal.ppat.1007012 Chen, 2016, HMBA enhances prostratin-induced activation of latent HIV-1 via suppressing the expression of negative feedback regulator A20/TNFAIP3 in NF-κB signaling, Biomed Res Int, 2016 Geng, 2016, Development of an attenuated Tat protein as a highly-effective agent to specifically activate HIV-1 latency, Mol Ther, 24, 1528, 10.1038/mt.2016.117 Tang, 2018, Exosomal Tat protein activates latent HIV-1 in primary, resting CD4+ T lymphocytes, JCI Insight, 3, 10.1172/jci.insight.95676 Sgadari, 2019, Continued decay of HIV proviral DNA upon vaccination with HIV-1 Tat of subjects on long-term ART: an 8-year follow-up study, Front Immunol, 10, 10.3389/fimmu.2019.00233 Boyer, 2018, Targeting immune checkpoint molecules to eliminate latent HIV, Front Immunol, 9, 2339, 10.3389/fimmu.2018.02339 Evans, 2018, Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency, AIDS, 32, 1491, 10.1097/QAD.0000000000001849 Fromentin, 2019, PD-1 blockade potentiates HIV latency reversal ex vivo in CD4+ T cells from ART-suppressed individuals, Nat Commun, 10, 10.1038/s41467-019-08798-7 Bui, 2019, Blockade of the PD-1 axis alone is not sufficient to activate HIV-1 virion production from CD4+ T cells of individuals on suppressive ART, PLoS One, 25 Grau-Expósito, 2017, A novel single-cell FISH-Flow assay identifies effector memory CD4+ T cells as a major niche for HIV-1 transcription in HIV-infected patients, mBio, 8, 10.1128/mBio.00876-17 Rao, 2018, The RNA surveillance proteins UPF1, UPF2 and SMG6 affect HIV-1 reactivation at a post-transcriptional level, Retrovirology, 28, 42, 10.1186/s12977-018-0425-2 Sarracino, 2018, Posttranscriptional regulation of HIV-1 gene expression during replication and reactivation from latency by nuclear matrix protein MATR3, mBio, 9, 10.1128/mBio.02158-18 Cheung, 2016, Parallel synthesis approach to the identification of novel diheteroarylamide-based compounds blocking HIV replication: potential inhibitors of HIV-1 Pre-mRNA alternative splicing, J Med Chem, 59, 1869, 10.1021/acs.jmedchem.5b01357 Kyei, 2018, Splicing factor 3B subunit 1 interacts with HIV Tat and plays a role in viral transcription and reactivation from latency, mBio, 9, 10.1128/mBio.01423-18 Mediouni, 2019, Didehydro-Cortistatin A inhibits HIV-1 by specifically binding to the unstructured basic region of Tat, mBio, 10, e02662-1, 10.1128/mBio.02662-18 Li, 2019, Tat inhibition by didehydro-Cortistatin A promotes heterochromatin formation at the HIV-1 long terminal repeat, Epigenetics Chromatin, 12, 23, 10.1186/s13072-019-0267-8 Besnard, 2016, The mTOR complex controls HIV latency, Cell Host Microbe, 20, 785, 10.1016/j.chom.2016.11.001 Wong, 2018, Cardiac glycoside/aglycones inhibit HIV-1 gene expression by a mechanism requiring MEK1/2-ERK1/2 signaling, Sci Rep, 8 Balachandran, 2017, Identification of small molecule modulators of HIV-1 Tat and Rev protein accumulation, Retrovirology, 14, 7, 10.1186/s12977-017-0330-0 Vautrin, 2019, Both anti-inflammatory and antiviral properties of novel drug candidate ABX464 are mediated by modulation of RNA splicing, Sci Rep, 9, 10.1038/s41598-018-37813-y Debyser, 2018, Insight in HIV integration site selection provides a block-and-lock strategy for a functional cure of HIV infection, Viruses, 11, 10.3390/v11010012 Kim, 2018, Getting the “kill” into “shock and kill”: strategies to eliminate latent HIV, Cell Host Microbe, 23, 14, 10.1016/j.chom.2017.12.004 Bobardt, 2019, The inhibitor apoptosis protein antagonist Debio 1143 Is an attractive HIV-1 latency reversal candidate, PLoS One, 14, 10.1371/journal.pone.0211746 Campbell, 2018, SMAC mimetics induce autophagy-dependent apoptosis of HIV-1-infected resting memory CD4+ T cells, Cell Host Microbe, 24, 689, 10.1016/j.chom.2018.09.007 Cummins, 2017, Maintenance of the HIV reservoir is antagonized by selective BCL2 inhibition, J Virol, 91, 10.1128/JVI.00012-17 Li, 2016, Stimulating the RIG-I pathway to kill cells in the latent HIV reservoir following viral reactivation, Nat Med, 22, 807, 10.1038/nm.4124 Garcia-Vidal, 2017, Evaluation of the innate immune modulator acitretin as a strategy to clear the HIV reservoir, Antimicrob Agents Chemother, 61, 10.1128/AAC.01368-17 Battivelli, 2018, Distinct chromatin functional states correlate with HIV latency reactivation in infected primary CD4+ T cells, eLife, 7, 10.7554/eLife.34655