Accessible Requires Authentication Published by De Gruyter October 31, 2017

Therapeutic strategies to fight HIV-1 latency: progress and challenges

Sello Lebohang Manoto, Lebogang Thobakgale, Rudzani Malabi, Charles Maphanga, Saturnin Ombinda-Lemboumba and Patience Mthunzi-Kufa
From the journal Biologia


The life-long persistence of human immunodeficiency virus type-1 (HIV-1) in latent reservoirs is a major hurdle in the eradication of HIV-1, even though highly active antiretroviral therapy (HAART) can be effective in reducing the plasma HIV-1 RNA to less than 50 copies per mL, which is below the detection limit of most clinical assays. In the latent reservoirs the provirus is integrated in the host genome but does not actively replicate and thus is not inhibited by HAART or recognized by the host immune system. There has been increasing scientific interest and investment into research towards HIV cure due to the challenges and limitation of life long treatment. The various strategies that have been developed aim to activate gene expression in HIV latent cells which might lead to the elimination of the virus by HAART or the immune system. In this review we discuss latency and therapeutic approaches that are being evaluated to eradicate HIV latently infected cells to overcome the burden of life long HAART. In addition, we explore the possibility of delivering HAART in latently infected cells using femtosecond laser pulses, a topic closely studied in our research.


The authors thank the Council for Scientific and Industrial Research and the Department of Science and Technology of South Africa for providing support.


Abbas W. & Herbein G. 2012. Molecular understanding of HIV-1 latency. Adv. Virol. 2012: Article ID: 574967.22548060 Search in Google Scholar

Archin A.M., Sung J.M., Garrido C., Soriano-Sarabia N. & Margolis D.M. 2014. Eradicating HIV-1 infection: seeking to clear a persistent pathogen. Nature Rev. Microbiol. 12: 750–764.10.1038/nrmicro3352 Search in Google Scholar

Archin N.M., Liberty A.L., Kashuba A.D., Choudhary S.K., Kuruc J.D., Crooks A.M., Parker D.C., Anderson E.M., Kearney M.F, Strain M.C., Richman D.D., Hudgens M.G., Bosch R.J., Coffin J.M., Eron J.J., Hazuda D.J. & Margolis D.M. 2012. Administration of vorinostat disrupts HIV-1 latency in patients on antiretroviral therapy. Nature 487: 482–485.10.1038/nature1128622837004 Search in Google Scholar

Banerjee C., Archin N., Michaels D., Belkina A.C., Denis G.V., Bradner J., Sebastiani P., Margolis D.M. & Montano M. 2012. BET bromodomain inhibition as a novel strategy for reactivation of HIV-1. J. Leukoc. Biol. 92: 1147–1154.10.1189/jlb.031216522802445 Search in Google Scholar

Barouch D.H., Whitney J.B., Moldt B., Klein F., Oliveira T.Y., Liu J., Stephenson K.E., Chang H., Shekhar K., Gupta S., Nkolola J.P., Seaman M.S., Smith K.M, Borducchi E.N., Cabral C., Smith J.Y., Blackmore S., Sanisetty S., Perry J.R., Beck M., Lewis M.G., Rinaldi W., Chakraborty A.K., Poignard P., Nussenzweig M.C. & Burton D.R. 2013. Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-infected rhesus monkeys. Nature 503: 224–228.24172905 Search in Google Scholar

Barre-Sinoussi F., Cherman J.C., Rey F., Nugeyre M.T., Chamaret S., Gruest J., Dauguet C., Axler-Blin C., Vezinet-Brun F., Rouzioux C., Rozenbaum W. & Montagnier L. 1983. Isolation of a T-lymphotropic retrovirus from a patient at risk for acquired immune deficiency syndrome (AIDS). Science 220: 868–871.10.1126/science.61891836189183 Search in Google Scholar

Battistini A. & Sgarbanti M. 2014. HIV-1 latency: an update of molecular mechanisms and therapeutic strategies. Viruses 6: 1715–1758.10.3390/v604171524736215 Search in Google Scholar

Baumgart J., Bintig W., Ngezahayo A., Lubatschowski H. & Heisterkamp A. 2010. Fs-laser-induced Ca2+ concentration change during membrane perforation for cell transfection. Opt. Express 18: 2219–2229.10.1364/OE.18.00221920174050 Search in Google Scholar

Bernhard W., Barreto K., Saunders A., Dahabieh M.S., Johnson P. & Sadowski I. 2011. The Suv39H1 methyltransferase inhibitor chaetocin causes induction of integrated HIV-1 without producing a T cell response. FEBS Lett. 585: 3549–3554.10.1016/j.febslet.2011.10.018 Search in Google Scholar

Blankson J.N., Persaud D. & Siliciano R.F. 2002. The challenge of viral reservoirs in HIV-1 infection. Ann. Rev. Med. 53: 557–593.10.1146/ Search in Google Scholar

Boulais E., Lachaine R., Hatef A. & Meunier M. 2013. Plasmonics for pulsed-laser cell nanosurgery: fundamentals and applications. J. Photochem. Photobiol. C Photochem. Rev. 17: 26–49.10.1016/j.jphotochemrev.2013.06.001 Search in Google Scholar

Bour S., Geleziunas R. & Wainberg M.A. 1995. The human immunodeficiency virus type 1 (HIV-1) CD4 receptor and its central role in promotion of HIV-1 infection. Microbiol. Rev. 59: 63–93.7708013 Search in Google Scholar

Choi B.S., Lee H.S., Oh Y.T, Hyun Y.L., Ro S., Kim S.S. & Hong K.J. 2010. Novel histone deacetylase inhibitors CG05 and CG06 effectively reactivate latently infected HIV-1. AIDS 24: 609–611.2015458210.1097/QAD.0b013e328333bfa1 Search in Google Scholar

Chomont N., El-Far M., Ancuta P., Trautman L., Procopio F.A, Yassine-Diab B., Boucher G., Boulassel M., Ghattas G., Brenchley J.M., Schacker T.W., Hill B.J, Douek D.C., Routy J.P., Haddad E.K. & Sekaly R. 2009. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nature Med. 15: 893–900.10.1038/nm.1972 Search in Google Scholar

Churchill M.J., Wesselingh S.L., Cowley D., Pardo C.A., McArthur J.C., Brew B.J. & Gorry P.R. 2009. Extensive astrocyte infection is prominent in human immunodeficiency virus associated dementia. Ann. Neurol. 66: 253–258.1974345410.1002/ana.21697 Search in Google Scholar

Ciuffi A., Mohammadi P., Golumbeanu M., di Iulio J. & Telenti A. 2015. Bioinformatics and HIV latency. Curr. HIV/AIDS Rep. 12: 97–106.2558614610.1007/s11904-014-0240-x Search in Google Scholar

Coiras M., Lopez-Huertas M.R., Perez-Olmeda M. & Alcami J. 2009. Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nature Rev. Microbiol. 7: 798–812.10.1038/nrmicro2223 Search in Google Scholar

Contreras X., Schweneker M., Chen C.S., McCune J.M., Deeks S.G, Martin J. & Peterlin B.M. 2009. Suberoylanilde hydroxamic acid reactivates HIV from latently infected cells. J. Biol. Chem. 284: 6782–6789.10.1074/jbc.M80789820019136668 Search in Google Scholar

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: 1459–1469.17937499 Search in Google Scholar

Dampier W., Nonnemacher M.R., Sullivan N.T., Jacobson J.M. & Wigdahl B. 2014. HIV excision utilizing CRISPRr/cas9 technology: attacking the proviral quasispecies in reservoirs to achieve a cure. MOJ Immunol. 1: pii00022. Search in Google Scholar

Deeks S.G., Autran B., Berkhout B., Benkirane M., Cairns S., Chomont N., Chun T.W., Churchill M., Di Mascio M., Katlama C., Lafeuillade A., Landay A., Lederman M., Lewin S.R., Maldarelli F., Margolis D., Markowitz M., Martinez-Picado J., Mullins J.I., Mellors J., Moreno S., O’Doherty U., Palmer S., Penicaud M.C., Peterlin M., Poli G., Routy J.P., Rouzioux C., Silvestri G., Stevenson M., Telenti A., Van Lint, C., Verdin E., Woolfrey A., Zaia J. & Barré-Sinoussi F. 2012. Towards an HIV cure: a global scientific strategy. Nat. Rev. Immunol. 12: 607–614.10.1038/nri3262 Search in Google Scholar

Deleage C., Moreau M., Rioux-Leclercq N., Ruffault A., Jegou B. & Dejucq-Rainsford N. 2011. Human immunodeficiency virus infects human seminal vesicles in vitro and in vivo. Am. J Pathol. 179: 2397–2408.10.1016/j.ajpath.2011.08.00521925468 Search in Google Scholar

Deng K., Pertea M., Rongvaux A., Wang L., Durand C.M., Ghiaur G., Lai J., McHugh H.L., Hao H., Zhang H., Margolick J.B., Gurer C., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Deeks S.G., Strowig T., Kumar P., Siliciano J.D., Salzberg S.L., Flavell R.A., Shan L. & Siliciano R.F. 2015. Broad CTL response is required to clear latent HIV-1 due todominance of escape mutations. Nature 517: 381–385.2556118010.1038/nature14053 Search in Google Scholar

Dykhuizen E.C., Carmody L.C., Tolliday N., Crabtree G.R., Palmer M.A. 2012. Screening for inhibitors of an essential chromatin remodeler in mouse embryonic stem cells by monitoring transcriptional regulation. J. Biomol. Screen. 17: 1221–1230.10.1177/108705711245506022853929 Search in Google Scholar

Fernandez G. & Zeichner S.L. 2010. Cell line dependent variability in HIV activation employing DNMT inhibitors. Virol. J. 7: 266.10.1186/1743-422X-7-26620942961 Search in Google Scholar

Forthal D., Hope T.J. & Alter G. 2013. New paradigms for functional HIV-specific nonneutralizing antibodies. Curr. Opin. HIV/AIDS 8: 393–401. Search in Google Scholar

Friedman J., Cho W.K., Chu C.K., Keedy K.S, Archin N.M., Margolis D.M. & Karn J. 2011. Epigenetic silencing of HIV-1 by the histone H3 lysine 27 methyltransferase enhancer of Zeste 2. J. Virol. 85: 9078–9089.2171548010.1128/JVI.00836-11 Search in Google Scholar

Fry T.J. & Mackall C.L. 2002. Interleukin-7: from bench to clinic. Blood 99: 3892–3904.10.1182/blood.V99.11.389212010786 Search in Google Scholar

Grah E.H., Pace M.J., Peterson B.A, Lynch L.J, Chukwulebe S.B., Mexas A.M., Shaheen F., Martin J.N., Deeks S.G., Connors M., Migueles S.A. & O’Doherty U. 2013. Gag positive reservoir cells are susceptible to HIV specific cytotoxic T lymphocyte mediated clearance in vitro and can be detected in vivo. Plos One 8: e71879.2395126310.1371/journal.pone.0071879 Search in Google Scholar

Halper-Stromberg A., Lu C.L., Klein F., Horwitz J.A., Bournazos S., Nogueira L., Eisenreich T.R, Liu C., Gazumyan A., Schaefer U., Furze R.C., Seaman M.S., Prinjha R., Tarakhovs A., Ravetch J.V. & Nussenzweig M.C. 2014. Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell 158: 989–999.10.1016/j.cell.2014.07.043 Search in Google Scholar

Hersperger A.R., Migueles S.A., Bett M.R. & Connors M. 2011. Qualitative features of the HIV-specific CD8+ T-cell response associated with immunologic control. Curr. Opin. HIV AIDS 6: 169–173.10.1097/COH.0b013e3283454c3921399496 Search in Google Scholar

Horwitz J.A., Halper-Stromberga A., Mouqueta H., Gitlina A.D., Tretiakovac A., Eisenreicha T.R., Malbecd M., Gravemanne S., Billerbeckf E., Dornerf M., Büninge H., Schwartzd O., Knopse E., Kaisere R., Seamang M.S., Wilsonc J.M., Ricef C.M., Plossf A., Bjorkmani J., Kleina F. & Nussenzweig M.C. 2013. HIV-1 suppression and durable control by combining single broadly neutralizing antibodies and antiretroviral drugs in humanized mice. Proc. Natl. Acad. Sci. USA 110: 16538–16543.10.1073/pnas.1315295110 Search in Google Scholar

Huber K., Doyon G., Plaks J., Fyne E., Mellors J.W., & Sluis-Cremer N. 2011. Inhibitors of histone deacetylases: correlation between isoform specificity and reactivation of HIV type 1 (HIV-1) from latently infected cells. J Biol. Chem. 286: 22211–22218.2153171610.1074/jbc.M110.180224 Search in Google Scholar

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: 16538–16545.2033516310.1074/jbc.M110.103531 Search in Google Scholar

Jones R.B., O’Connor R., Mueller S., Foley M., Szeto G.L., Karel D., Lichterfeld M., Kovacs C., Ostrowski M.A., Trocha A., Irvine D.J. & Walker B.D. 2014. Histone deacetylase inhibitors impair the elimination of HIV-infected cells by cytotoxic T-lymphocytes. PLoS Pathog. 10: e1004287.2512221910.1371/journal.ppat.1004287 Search in Google Scholar

Junt T. & Barchet W. 2015. Translating nucleic acid sensing pathways into therapies. Nat. Rev. Immunol. 15: 529–544.2629263810.1038/nri3875 Search in Google Scholar

Katlama C., Deeks S.G., Autran B., Martinez-Picado J., van Lunzen J., Rouzioux C., Miller M., Vella S., Schmitz J.E., Ahlers J., Richman D.D. & Sekaly R.P. 2013. Barriers to a cure for HIV: new ways to target and eradicate HIV-1 reservoirs. Lancet 381: 2109–2117.10.1016/S0140-6736(13)60104-X23541541 Search in Google Scholar

Kashanchi F., Melpolder J.C., Epstein J.S. & Sadaie M.R. 1997. Rapid and sensitive detection of cell associated HIV-1 in latently infected cell lines and in patient cells using sodium n butyrate induction and RT-PCR. J. Med. Virol. 52: 179–189.10.1002/(SICI)1096-9071(199706)52:2<179::AID-JMV11>3.0.CO;2-G9179766 Search in Google Scholar

Kauder S.E., Bosque A., Lindqvist A., Planells V. & Verdin E. 2009. Epigenetic regulation of HIV-1 latency by cytosine methylation. PloS Pathog. 5: e1000495.10.1371/journal.ppat.100049519557157 Search in Google Scholar

Kulkosky J., Sullivan J., Xu Y., Sounder E., Hamer D.H. & Pomerantz R.J. 2004. Expression of latent HAART persistent HIV type 1 induced by novel cellular activating agents. AIDS Res. Hum. Retroviruses 20: 497–505.10.1089/08892220432308774115186524 Search in Google Scholar

Kumar A., Abbas W. & Herbein G. 2014. HIV-1 latency in monocytes/macrophages. Viruses 6: 1837–1860.2475921310.3390/v6041837 Search in Google Scholar

Lam S., Sung J., Cruz C., Castillo-Caro P., Ngo M., Garrido C., Kuruc J., Archin N., Rooney C., Margolis D. & Bollard C. 2015. Broadly-specific cytotoxic T cells targeting multiple HIV antigens are expanded from HIV+ patients: implications for immunotherapy. Mol. Ther. 23: 387–395.2536603010.1038/mt.2014.207 Search in Google Scholar

Lassen K., Han Y., Zhou Y., Siliciano J. & Siliciano R.F. 2004. The multifactorial nature of HIV-1 latency. Trends Mol. Med. 10: 525–531.1551927810.1016/j.molmed.2004.09.006 Search in Google Scholar

Lu H.K., Gray L.R., Wightman F., Ellenberg P., Khoury G., Cheng W.J., Mota T.M., Wesselingh S., Gorry P.R., Cameron P. U., Churchill M.J., Lewin S.R. 2014. Ex vivo response to histone deacetylase (HDAC) inhibitors of the HIV long terminal repeat (LTR) derived from HIV-infected patients on antiretroviral therapy. PLoS One 9: e113341.2540933410.1371/journal.pone.0113341 Search in Google Scholar

Lu P., Qu X., Shen Y., Jiang Z., Wang P., Zeng H., Ji H., Deng J., Yang X., Li X., Lu H & Zhu H. 1996. The BET inhibitor OTX015 reactivates latent HIV-1 through p-TEFb. Sci. Rep. 6: 24100. Search in Google Scholar

Lusic M. & Giacca M. 2015. Regulation of HIV-1 latency by chromatin structure and nuclear architecture. J. Mol. Biol. 457: 688–694. Search in Google Scholar

Malabi R., Manoto S., Ombinda-Lemboumba S., Maaza M. & Mthunzi-Kufa P. 2017. In vitro photo-translocation of antiretroviral drug delivery into TZMbl cell. Proc. SPIE 10062: 1006204.10.1117/12.2252238 Search in Google Scholar

Marcello A. 2006. Latency: the hidden HIV-1 challenge. Retrovirology 3: 7.16412247 Search in Google Scholar

Matalon S., Palmer B.E., Nold M.F., Furlan A., Kassu A., Fossati G., Mascagni P. & Dinarello C.A. 2010. The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4+ T cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro. J. Acquir. Immune Defic. Syndr. 54: 1–9.20300007 Search in Google Scholar

Mbonye U. & Karn J. 2014. Transcriptional control of HIV latency: cellular signalling pathways, epigenetics, happenstance and the hope for a cure. Virology 454-455: 328–339.10.1016/j.virol.2014.02.008 Search in Google Scholar

Mehla R., Bivalkar-Mehla S., Zhang R., Handy I., Albrecht H., Giri S., Nagarkatti P., Nagarkatti M. & Chauhan A. 2010. Bryostatin modulates latent HIV-1 infection via PKC and AMPK signalling but inhibits acute infection in a receptor independent manner. PLoS One 5: e11160.10.1371/journal.pone.0011160 Search in Google Scholar

Mthunzi P., Dholakia K. & Gunn-Moore F. 2010. Phototransfection of mammalian cells using femtosecond laser pulses: optimization and applicability to stem cell differentiation. J. Biomed. Optics 15: 1–7. Search in Google Scholar

Mthunzi P., He K., Ngcobo S. & Warner J.W. 2014. Enhanced photo-transfection efficiency of mammalian cells on graphene coated substrates. Proc. SPIE 8944: 89440K. Search in Google Scholar

Mussolino C., Morbitzer R., Lütge F., Dannemann N., Lahaye T. & Cathomen T. 2011. A novel TALE nuclease scaffold enables high genome editing activity in combination with low toxicity. Nucleic Acids Res. 39: 9283–9293.2181345910.1093/nar/gkr597 Search in Google Scholar

Narlikar G.J., Sundaramoorthy R. & Owen-Hughes T. 2013. Mechanisms and functions of ATP dependent chromatin remodelling enzymes. Cell 154: 490–503.2391131710.1016/j.cell.2013.07.011 Search in Google Scholar

Pegu A., Asokan M., Wu L., Wang K., Hataye J., Casazza J.P., Guo X., Shi W., Georgiev I., Zhou T., Chen X., O’Dell S., Todd J., Kwong P.D., Rao S.S., Yang Z., Koup R.A., Mascola J.R. & Nabel G.J. 2015. Activation and lysis of human CD4 cells latently infected with HIV-1. Nature Commun. 6: 1–9. Search in Google Scholar

Phillips A.N, Neaton, J. & Ludgren, J.D. 2008. The role of HIV in serious diseases other than AIDS. AIDS 22: 2409–2418.10.1097/QAD.0b013e328317463619005264 Search in Google Scholar

Praveen B.B., Stevenson D.J., Antkowiak M., Dholakia K. & Gunn-Moore F.J. 2011. Enhancement and optimization of plasmid expression in femtosecond optical transfection. J. Biophotonics 4: 229–235.2144601210.1002/jbio.201000105 Search in Google Scholar

Reuse S., Calao M., Kabeya K., Guiguen A., Gatot J.S., Quivy V., Vanhulle C., Lamine A., Vaira D., Demonte D., Martinelli V., Veithen E., Cherrier T., Avettand V., Poutrel S., Piette J., de Launoit Y., Moutschen M., Burny A., Rouzioux C., De Wit S., Herbein G., Rohr O., Collette Y., Lambotte O., Clumeck N. & Van Lint C. 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.000609319564922 Search in Google Scholar

Saksena N.K., Wang B., Zhou L., Soedjono M., Ho Y.S. & Conceicao V. 2010. HIV reservoirs in vivo and new strategies for possible eradication of HIV from the reservoir sites. HIV AIDS 2: 103–122. Search in Google Scholar

Saleh S., Solomon A., Wightman F. & Xhilaga M. 2007. Cameron PU, Lewin SR. CCR7 ligands CCL19 and CCL21 increase permissiveness of resting memory CD4+ T cells to HIV-1 infection: a novel model of HIV-1 latency. Blood 110: 4161–4164.10.1182/blood-2007-06-09790717881634 Search in Google Scholar

Schiffer J.T., Aubert M., Weber N.D, Mintzer E., Stone D. & Jerome K.R. 2012. Targeted DNA mutagenesis for the cure of chronic viral infections. J. Virol. 86: 8920–8936.2271883010.1128/JVI.00052-12 Search in Google Scholar

Shan L. & Siliciano R.F. 2013. From reactivation of latent HIV-1 to elimination of the latent reservoir: the presence of multiple barriers to viral eradication. BioEssays 35: 544–552.10.1002/bies.20120017023613347 Search in Google Scholar

Shang H., Ding J., Yu S., Wu T., Zhang Q. & Liang F. 2015. Progress and challenges in the use of latent HIV-1 reactivating agents. Acta Pharmacol. Sin. 36: 908–916.10.1038/aps.2015.22 Search in Google Scholar

Shirakawa K., Chavez L., Hakre S., Calvanese V. & Verdin E. 2013. Activation of latent HIV by histone deactylases inhibitors. Trends Micobiol. 21: 277–285.10.1016/j.tim.2013.02.005 Search in Google Scholar

Sierra S., Kupfer B. & Kaiser R. 2005. Basics of the virology of HIV-1 and its replication. J. Clin. Virology 34: 233–244.10.1016/j.jcv.2005.09.004 Search in Google Scholar

Siliciano J.D., Kajdas J., Finzi D., Quinn T.C., Chadwick K., Margolick J.B, Kovacs C, Gange S.J. & Siliciano R.F. 2003. Long term follow up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat. Med. 9: 727–728.1275450410.1038/nm880 Search in Google Scholar

Siliciano J.M. & Siliciano R.F. 2015. The remarkable stability of the latent reservoir for HIV-1 in resting memory CD4+ T cells. J. Infect. Dis. 212: 1345–1347.2587755110.1093/infdis/jiv219 Search in Google Scholar

Siliciano R.F. & Greene W.C. 2011. HIV latency. Cold Spring Harb. Perspect. Med. 1: 1–19. Search in Google Scholar

Stoszko M., De Crignis E., Rokx C., Khalid M.M., Lungu C., Palstra R., Kan T.W., Boucher C., Verbon A., Dykhuizen E.C. & Mahmoudi T. 2016. Small molecule inhibitors of BAF; a promising family of compounds in HIV-1 latency reversal. EBioMedicine 3: 108–121.2687082210.1016/j.ebiom.2015.11.047 Search in Google Scholar

Tebas P., Stein D., Tang W.W., Frank I., Wang S.Q., Lee G., Spratt S.K., Surosky R.T, Giedlin M.A., Nichol G., Holmes M.C., Gregory P.D., Ando D.G., Kalos M., Collman R.G., Binder-Scholl G., Plesa G., Hwang W.T., Levine B.L. & June C.H. 2014. Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N. Engl. J Med. 370: 901–910.10.1056/NEJMoa130066224597865 Search in Google Scholar

Terasaki M., Miyake K. & McNeil P.L. 1997. Large plasma membrane disruptions are rapidly resealed by Ca2+ dependent vesicle-vesicle fusion events. J. Cell Biol. 139: 63–74.931452910.1083/jcb.139.1.63 Search in Google Scholar

Togo T. 2006. Disruption of the plasma membrane stimulates rearrangement of microtubules and lipid traffic toward the wound site. J. Cell Sci. 119: 2780–2786.1677233510.1242/jcs.03006 Search in Google Scholar

Tsai A., Irrinki A., Kaur J., Cihlar T., Kukolj G., Sloan D.D. & Murry J.P. 2017. Toll-like receptor 7 agonist GS-9620 induces HIV expression and HIV-specific immunity in cells from HIV-infected individuals on suppressive antiretroviral therapy. J. Virol. 91: 1–19. Search in Google Scholar

Turner L.S., Tsygankov A.Y. & Henderson E.E. 2006. StpC-based gene therapy targeting latent reservoirs of HIV-1. Antiviral Res. 72: 233–241.10.1016/j.antiviral.2006.06.01016891001 Search in Google Scholar

Van Lint C., Emiliani S. & Verdin E. Trascriptional activation and chromatin remodelling of the HIV-1 promoter in response to histone acetylation. EMBO J. 15: 1112–1120. Search in Google Scholar

Verdin E., Paras P. & Van Lint C. Chromatin disruption in the promoter of human immunodeficiency virus type 1 during transcriptional activation. EMBO J. 12: 3249–3259.8344262 Search in Google Scholar

Vlach J. & Pitha P.M. 1993. Hexamethylene bisacetamide activates the human immunodeficiency virus type 1 provirus by an NF-kappa B-independent mechanism. J. Gen. Virol. 74: 2401–2408.10.1099/0022-1317-74-11-24018245855 Search in Google Scholar

Vogel A., Noack J., Nahen K., Theisen D., Busch S., Parlitz U., Hammer D.X., Noojin G.D., Rockwell B.A. & Birngruber R. 1999. Energy balance of optical breakdown in water at nanosecond to femtosecond time scales. Appl. Phys. B: Lasers Optics 68: 271–280.10.1007/s003400050617 Search in Google Scholar

Waleed M., Hwang S.U., Kim J.D., Shabbir I., Shin S.M. & Lee Y.G. 2013. Single-cell optoporation and transfection using femtosecond laser and optical tweezers. Biomed. Opt. Express 4: 1533–1547.10.1364/BOE.4.00153324049675 Search in Google Scholar

Warrilow D., Gardner J., Darnell G.A., Suhrbier A. & Harrich D. 2006. HIV type 1 inhibition by protein kinase C modulatory compounds. AIDS Res. Hum. Retroviruses 22: 854–864.10.1089/aid.2006.22.85416989610 Search in Google Scholar

Wei D.G., Chiang V., Fyne E., Balakrishnan M., Barnes T., Graupe M., Hesselgesser J., Irrinki A., Murry J.P., Stepan G., Stray K.M., Tsai A., Yu H., Spindler J., Kearney M., Spina C.A., McMahon D., Lalezari J., Sloan D., Mellors J., Geleziunas R. & Cihlar T. 2014. Histone deacetylase inhibitor romidepsin induces HIV expression in CD4 T cells from patients on suppressive antiretroviral therapy at concentrations achieved by clinical dosing. PLoS Pathog. 10: e1004071.10.1371/journal.ppat.100407124722454 Search in Google Scholar

Williams S.A., Chen L.F., Kwon H., Fernard D., Bisgrove D., Verdin E. & Greene W.C. 2004. Prostratin antagonizes HIV latency by activating NF-κB. J Biol. Chem. 279: 42008–420017.1528424510.1074/jbc.M402124200 Search in Google Scholar

Williams S.A. & Greene W.C. 2007. Regulation of HIV-1 latency by T cell activation. Cytokine 39: 63–74.10.1016/j.cyto.2007.05.017 Search in Google Scholar

Xing S., Bullen C.K., Shroff N.S., Shan L., Yang H.C., Manucci J.L., Bhat S., Zhang H., Margolick J.B., Quinn T.C., Margolis D.M., Siliciano J.D. & Siliciano R.F. 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 Search in Google Scholar

Xing S. & Siliciano R.F. 2013. Targeting HIV latency: pharmacologic strategies toward eradication. Drug Discov. Today 18: 541–551.10.1016/j.drudis.2012.12.00823270785 Search in Google Scholar

Yin H., Zhang Y., Zhou X. & Zhu H. 2011. Histone deacetylase inhibitor oxamflatin increase HIV-1 transcription by inducing histone modification in latently infected cells. Mol. Biol. Rep. 38: 5071–5078.2118127210.1007/s11033-010-0653-6 Search in Google Scholar

Zhang Z., Fu J., Zhao Q., He Y., Jin L, Zhang H., Yao J., Zhang L. & Wang F.S. 2006. Differential restoration of myeloid and plasmacytoid dendritic cells in HIV-1 infected children after treatment with highly active antiretroviral therapy. J. Immunol. 176: 5644–5651.1662203410.4049/jimmunol.176.9.5644 Search in Google Scholar

Zysset B., Fujimoto J.G., Puliafito C.A. Birngruber R & Thomos F.D. 1989. Picosecond optical breakdown: tissue effects and reduction of collateral damage. Lasers Surg. Med. 9: 193–204.10.1002/lsm.19000903022659910 Search in Google Scholar



acquired immune deficiency syndrome


activator protein 1


BRG-Brahma associated factors


BAF inhibitors


broadly neutralizing antibodies




bromodomain and extraterminal domain


cyclin dependent kinase 9


central nervous system


chicken ovalbumin upstream promoter


clustered regularly interspaced short palindromic repeats


cytotoxic T lymphocytes


cyclin T1


DNA methyltransferase inhibitors


highly active antiretroviral therapy


histone deacetylase inhibitors


histone deacetylases


HMBA-induced protein 1


hexamethylene bisacetamide


histone methyltransferase inhibitors


histone methyltransferases


Herpes Simplex Virus


inhibitor of kappa B alpha




Janus kinase


long terminal repeat


methyl-CpG binding domain protein 2


nuclear factor 1


nuclear factor of activated T cells


nuclear factor kappa B


programmed cell death protein 1


protein kinase C


positive transcription elongation factor b


small interfering RNA


specificity protein 1


signal transducer and activator of transcription


transcription factor 1 alpha


thymidine kinase


toll-like receptors


upstream binding protein 1


upstream stimulatory factor

Received: 2017-5-12
Accepted: 2017-10-22
Published Online: 2017-10-31
Published in Print: 2017-10-26

© 2017 Institute of Molecular Biology, Slovak Academy of Sciences