Unique natural and adaptive response mechanisms to control and eradicate HIV infection

Daniel Amsterdam; Daniel Amsterdam

doi:10.3934/Allergy.2018.3.113

AIMS Allergy and Immunology

2018, Volume 2, Issue 3: 113-125. doi: 10.3934/Allergy.2018.3.113

Previous Article Next Article

Review

Unique natural and adaptive response mechanisms to control and eradicate HIV infection

Daniel Amsterdam ^,

Departments of Microbiology & Immunology, Medicine & Pathology, Jacobs School of Medicine & Biomedical Sciences, University at Buffalo, SUNY; Chief of Service, Laboratory Medicine, Erie County Medical Center Buffalo, NY, USA

Received: 30 May 2018 Accepted: 25 July 2018 Published: 31 July 2018

During the more than 35 years since the discovery of HIV as the causative agent of AIDS a preventative and/or therapeutic vaccine has not been achieved in spite of innovative and unique break-through discoveries in the diagnosis, monitoring of disease progression and pharmaceutical advances. In part the inability to cure HIV either through immunologic and/or pharmacologic approaches is a result of distinctive features of HIV-1 pathogens—the capability to persist in cryptic tissue reservoirs. Recent immunologic discoveries may lead to eradication of this virus. The recognition of adaptive immunologic approaches has led to the development of unique genome editing tools in the form of artificial nucleases that can and have been applied to the editing of selected HIV-1 genomic sequences. This review addresses recent developments in immuno-pharmacologic approaches in the form of inducing reversal agents, latency activation and gene editing which exemplify ongoing unique and imaginative efforts of investigators to achieve a “cure” for HIV/AIDS. The several strategies for the control and treatment of HIV with the aim of eradication of the virus from all tissue reservoirs are discussed.
- treatment of HIV,
- HIV infection,
- HIV latency,
- gene editing,
- CRISPR/Cas 9
Citation: Daniel Amsterdam. Unique natural and adaptive response mechanisms to control and eradicate HIV infection[J]. AIMS Allergy and Immunology, 2018, 2(3): 113-125. doi: 10.3934/Allergy.2018.3.113

Related Papers:

Abstract

During the more than 35 years since the discovery of HIV as the causative agent of AIDS a preventative and/or therapeutic vaccine has not been achieved in spite of innovative and unique break-through discoveries in the diagnosis, monitoring of disease progression and pharmaceutical advances. In part the inability to cure HIV either through immunologic and/or pharmacologic approaches is a result of distinctive features of HIV-1 pathogens—the capability to persist in cryptic tissue reservoirs. Recent immunologic discoveries may lead to eradication of this virus. The recognition of adaptive immunologic approaches has led to the development of unique genome editing tools in the form of artificial nucleases that can and have been applied to the editing of selected HIV-1 genomic sequences. This review addresses recent developments in immuno-pharmacologic approaches in the form of inducing reversal agents, latency activation and gene editing which exemplify ongoing unique and imaginative efforts of investigators to achieve a “cure” for HIV/AIDS. The several strategies for the control and treatment of HIV with the aim of eradication of the virus from all tissue reservoirs are discussed.

References

[1]	Center for Disease Control and Prevention (1981) Pneumocystis pneumonia. MMWR 30: 1–3.
[2]	Center for Disease Control and Prevention (2015) Prevalence of diagnosed and undiagnosed HIV infection-2008–2012. MMWR 64: 657–662.
[3]	Wainberg MA, Zaharatos GJ, Brenner BG (2010) Development of antiretroviral drug resistance. N Eng J Med 365: 637–645.
[4]	Maartens G, Celum C, Lewin SR (2014) HIV infection: epidemiology, pathogenesis, treatment, and prevention. Lancet 384: 258–271. doi: 10.1016/S0140-6736(14)60164-1
[5]	Huang Z, Tomitaka A, Raymond A, et al. (2017) Current application of CRISPR/Cas9 gene-editing technique to eradication of HIV/AIDS. Gene Ther 24: 377–384. doi: 10.1038/gt.2017.35
[6]	Chun TW, Engel D, Mizell SB, et al. (1998) Induction of HIV-1 replication in latently infected CD4+ T cells using a combination of cytokines. J Exp Med 188: 83–91. doi: 10.1084/jem.188.1.83
[7]	Finzi D, Hemankova M, Pierson T, et al. (1997) Identification of a reservoir for HIV-1 in patients on highly active antiretroviral therapy. Science 278: 1295–1300. doi: 10.1126/science.278.5341.1295
[8]	McElrath MJ, Steinman RM, Cohn ZA, et al. (1991) Latent HIV-1 infection in enriched populations of blood monocytes and T cells from seropositive patients. J Clin Inv 87: 27–30. doi: 10.1172/JCI114981
[9]	Chun TW, Engel D, Berrey MM, et al. (1998) Early establishment of a pool of latently infected, resting CD4 (+) T cells during primary HIV infection. PNAS 95: 8869–8873. doi: 10.1073/pnas.95.15.8869
[10]	Bagasra O, Lavi E, Bobroski I, et al. (1996) Cellular reservoirs of HIV-1 in the central nervous system of infected individuals: identification by the combination of in situ polymerase chain reaction and immunohistochemistry. AIDS 10: 573–585. doi: 10.1097/00002030-199606000-00002
[11]	Fischer-Smith T, Croul S, Sverstiuk AE, et al. (2001) CNS invasion by CD14+/CD16+ peripheral blood derived monocytes in HIV dementia: perivascular accumulation and reservoir of HIV infection. J Neurovirol 7: 528–541. doi: 10.1080/135502801753248114
[12]	Petito CK, Chen H, Mastri AR, et al. (1999) HIV infection of choroid plexus in AIDS and asymptomatic HIV infected patients suggests that choroid plexus might be a good reservoir of productive infection. J Neurovirol 5: 670–677. doi: 10.3109/13550289909021295
[13]	Chun TW, Carruth L, Finzi D, et al. (1997) Quantification of latent tissue reservoirs and total boy viral load in HIV-1 infection. Nature 387: 183–188. doi: 10.1038/387183a0
[14]	Chun TW, Nickle DC, Justement JS, et al. (2008) Persistence of HIV in gut-associated lymphoid tissue despite long-term antiretroviral therapy. J Inf Dis 197: 714–720. doi: 10.1086/527324
[15]	Smith PD, Meng G, Salazar-Gonzalez JF, et al. (2003) Macrophage HIV-1 infection and the potential gastrointestinal tract reservoir. J Leuk Bio 74: 642–649. doi: 10.1189/jlb.0503219
[16]	Lambert-Niclot S, Peytavin G, Duvivier C, et al. (2010) Low frequency of intermittent HIV-1 semen excretion on patients treated with darunavir-ritonavir at 600/100 milligrams twice a day plus two nucleoside reverse transcriptase inhibitors or monotherapy. Antimicrob Agents Chemo 54: 4910–4913. doi: 10.1128/AAC.00725-10
[17]	Cu-Uvin S, DeLong AK, Venkatesh KK, et al. (2010) Genital track HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS 24: 2489–2497. doi: 10.1097/QAD.0b013e32833e5043
[18]	Hutter G, Nowak D, Mossner M, et al. (2009) Long term control of HIV by CCR5 Delta 32/Delta 32 stem-cell transplantation. N Engl J Med 360: 692–968. doi: 10.1056/NEJMoa0802905
[19]	Perelson AS, Esunger P, Cao Y, et al. (1997) Decay characteristics of HIV-1 infected compartments during combination therapy. Nature 387: 188–191. doi: 10.1038/387188a0
[20]	Evering TH, Mehandru S, Racz P, et al. (2012) Absence of HIV-1 evolution in the gut-associated lymphoid tissue from patients on combination antiviral therapy initiated during primary infection. PLoS Pathog 8: e1002306.
[21]	Kearney MF, Spindler J, Shao W, et al. (2014) Lack of detectable HIV-1 molecular evolution during suppressive antiretroviral therapy. PLoS Pathog 10: e1004010. doi: 10.1371/journal.ppat.1004010
[22]	Cáceres CF, Mayer KH, Baggaley R, et al. (2015) PrEP implementation science: state-of-the-art and research agenda. J Int Aids Soc 18: 20527.
[23]	World Health Organization (2017) Implementation tool for pre-exposure prophylaxis (PrEP) of HIV infection. Policy Brief WHO Reference number: WHO/HIV/2017.19.
[24]	Chomont N, El-Far M, Ancuta P, et al. (2009) HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med 15: 893–900. doi: 10.1038/nm.1972
[25]	Kulpa DA, Lawani M, Cooper A, et al. (2013) PD-1 co-inhibitory signals: the link between pathogenesis and protection. Semin Immunol 25: 219–227. doi: 10.1016/j.smim.2013.02.002
[26]	Porichis F, Kaufmann DE (2012) Role of PD-1 in HIV-1 pathogenesis and as a target for therapy. Curr HIV-AIDS Rep 9: 81–90. doi: 10.1007/s11904-011-0106-4
[27]	Reguzova AY, Karpenko LI, Mechetina LV, et al. (2015) Peptide MHC multimer-based monitoring of CD8 T cells in HIV-1 infection and HIV vaccine development. Expert Rev Vaccines 14: 69–84. doi: 10.1586/14760584.2015.962520
[28]	Zhang JY, Zhang Z, Wang XZ, et al. (2007) PD-1 upregulation is correlated with HIV specific memory CD8 (+) T cells exhaustion in typical progressors but not in long-term non-progressors. Blood 109: 4671–4678. doi: 10.1182/blood-2006-09-044826
[29]	Cohen MS, Chen YQ, McCauley M, et al. (2016) Antiretroviral therapy for the prevention of HIV-1 transmission. N Engl J Med 375: 830–839. doi: 10.1056/NEJMoa1600693
[30]	Chun TW, Stuyver L, Misell SB, et al. (1997) Presence of an inducible HIV-1 latent reservoir during highly active antiretroviral therapy. PNAS 94: 13193–13197. doi: 10.1073/pnas.94.24.13193
[31]	Wong JK, Hezareh M, Gunthard HF, et al. (1997) Recovery of replication-competent HIV despite prolonged suppression of plasma viremia. Science 278: 1291–1295. doi: 10.1126/science.278.5341.1291
[32]	Finzi D, Blankson I, Siliciano JD, et al. (1999) Latent infection of CD4+ T cells provides a mechanism for lifelong persistence of HIV-1, even in patients on effective combination therapy. Nat Med 5: 512–517. doi: 10.1038/8394
[33]	Deeks SG (2012) HIV: shock and kill. Nature 487: 439–440. doi: 10.1038/487439a
[34]	Siliciano JD, Kajdas J, Finzi D, et al. (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. doi: 10.1038/nm880
[35]	Ruelas DS, Greene WC (2013) An integrated overview of HIV-1 latency. Cell 155: 519–529. doi: 10.1016/j.cell.2013.09.044
[36]	Donahue DA, Wainberg MA (2013) Cellular and molecular mechanisms involved in the establishment of HIV-1 latency. Retrovirology 10: 11. doi: 10.1186/1742-4690-10-11
[37]	Strain MC, Little SJ, Daar ES, et al. (2005) Effect of treatment during primary infection on establishment and clearance of cellular reservoirs of HIV-1. J Infect Dis 191: 1410–1418. doi: 10.1086/428777
[38]	Procopio FA, Fromentin R, Kulpa DA, et al. (2015) A novel assay to measure the magnitude of the inducible viral reservoir in HIV infected individuals. Ebiomedicine 2: 872–881.
[39]	Walker B, McMichael A (2012) The T-cell response to HIV. Cold Spring Harb Perspect Med 2: e007054.
[40]	Lia MK, Hawkins N, Ritchie AI, et al. (2013) CHAVI Core B. Vertical T cell immunodominance and epitope entropy determine HIV-1 escape. J Clin Invest 123: 380–393.
[41]	Ferrari G, Korber B, Goonetilde N, et al. (2011) Relationship between functional profile of HIV-1 specific CD8 T cells and epitope variability with the selection of escape mutants in acute HIV-1 infection. PLoS Pathog 7: e1001273. doi: 10.1371/journal.ppat.1001273
[42]	Streeck H, Brumme ZL, Anastario M, et al. (2008) Antigen load and viral sequence diversification determine the functional profile of HIV-1 specific CD8+ T cells. PLoS Med 5: e100. doi: 10.1371/journal.pmed.0050100
[43]	Pollana J, Nonsignori M, Moody MA, et al. (2013) Epitope specificity of human immunodeficiency virus-1 antibody dependent cellular cytotoxicity (ADCC) responses. Curr HIV Res 11: 378–387. doi: 10.2174/1570162X113116660059
[44]	Liao HX, Bonsignori M, Alam SM, et al. (2013) Vaccine induction of antibodies against a structurally heterogeneous site of immune pressure within HIV-1 envelope protein variable regions 1 and 2. Immunity 38: 176–186. doi: 10.1016/j.immuni.2012.11.011
[45]	Mascola JR, D'Souza P, Gilbert, et al. (2005) Recommendations for the design and use of standard virus panels to assess neutralizing antibody responses elicited by candidate human immunodeficiency virus type 1 vaccines. J Virol 79: 10103–10107. doi: 10.1128/JVI.79.16.10103-10107.2005
[46]	Xu L, Pegu A, Rao E, et al. (2017) Trispecific broadly neutralizing HIV antibodies mediate potent SHIV protection in macaques. Science 358: 85–90. doi: 10.1126/science.aan8630
[47]	Julg B, Liu PT, Wagh K, et al. (2017) Protection against a mixed SHIV challenge by a broadly neutralizing antibody cocktail. Sci Trans Med 9: eaao4235. doi: 10.1126/scitranslmed.aao4235
[48]	McCoy LE, Burton DR (2017) Identification and specificity of broadly neutralizing antibodies against HIV. Immunol Rev 275: 11–20. doi: 10.1111/imr.12484
[49]	Amsterdam D (2015) Immunotherapeutic approaches for the control and eradication of HIV. Immunol Inv 44: 719–730. doi: 10.3109/08820139.2015.1096680
[50]	Hirsch AJ (2010) The use of RNAi-based screens to identify host proteins involved in viral replication. Future Microbiol 5: 303–311. doi: 10.2217/fmb.09.121
[51]	Jacqua JM, Triques K, Stevenson M (2002) Modulation of HIV-1 replication by RNA interference. Nature 418: 435–438. doi: 10.1038/nature00896
[52]	Nishitsuji H, Kohara M, Kannagi M, et al. (2006) Effective suppression of human immunodeficiency virus type 1 through a combination of short- and long-hairpin RNAs targeting essential sequences for retroviral integration. J Virol 80: 7658–7666. doi: 10.1128/JVI.00078-06
[53]	Suzuki K, Ishida T, Yamagishi M, et al. (2011) Transcriptional gene silencing of HIV-1 through promoter targeting RNA is highly specific. RNA Biol 8: 1035–1046. doi: 10.4161/rna.8.6.16264
[54]	Taksuchi Y, Nagumo T, Hashino H (1988) Low fidelity of cell-free DNA synthesis by reverse transcriptase of human immunodeficiency virus. J Virol 62: 3000–3002.
[55]	Knoepfel SA, Centlivre M, Liu YP, et al. (2012) Selection of RNAi-based inhibitors for anti-HIV gene therapy. World J Virol 1: 79–90. doi: 10.5501/wjv.v1.i3.79
[56]	Anderson J, Akkina R (2005) CXCR4 and CCR5 shRNA transgenic CD34+ cell derived macrophages are functionally normal resist HIV-1 infection. Retrovirology 2: 53. doi: 10.1186/1742-4690-2-53
[57]	Martinez MA, Clotet B, Este JA (2002) RNA interference of HIV replication. Trends Immunol 3: 559–561.
[58]	Boutimah F, Eekels JJ, Liu YP, et al. (2013) Antiviral strategy combining antiretroviral drugs with RNAi-mediated attack on HIV-1 and cellular co-factors. Antiviral Res 98: 121–129. doi: 10.1016/j.antiviral.2013.02.011
[59]	Wolstein O, Boyd M, Millington M, et al. (2014) Preclinical safety and efficacy of an anti-HIV-1 lentiviral vector containing a short hairpin RNA to CCR5 and the C46 fusion inhibitor. Mol Ther Meth Clin Dev 1: 11. doi: 10.1038/mtm.2013.11
[60]	Cox DB, Platt RJ, Zhang F (2015) Therapeutic genome editing: Prospects and challenges. Nat Med 21: 121–131. doi: 10.1038/nm.3793
[61]	Badia R, Rivera-Munoz E, Clotet B, et al. (2014) Gene editing using a zinc-finger nuclease mimicking the CCR5Delta32 mutation induces resistance to CCR5-using HIV-1. J Antimicrob Chemother 69: 1755–1759. doi: 10.1093/jac/dku072
[62]	Perez EE, Wang J, Miller JC, et al. (2008) Establishment of HIV-1 resistance in CD4+ T cells by genome editing using zinc-finger nucleases. Nat Biotechnol 26: 808–816. doi: 10.1038/nbt1410
[63]	Yao Y, Nashun B, Zhou T, et al. (2012) Generation of CD34+ cells from CCR5-disrupted human embryonic and induced pluripotent stem cells. Hum Gene Ther 23: 238–242. doi: 10.1089/hum.2011.126
[64]	Wilen CB, Wang J, Tilton JC, et al. (2011) Engineering HIV-resistant human CD4+ T cells with CXCR4-specific zinc-finger nucleases. PLoS Pathog 7: e1002020. doi: 10.1371/journal.ppat.1002020
[65]	Didigu CA, Wilen CB, Wang J, et al. (2014) Simultaneous zinc-finger nuclease editing of HIV coreceptors ccr5 and cxcr4 protects CD4+ T cells from HIV-1 infection. Blood 123: 61–69. doi: 10.1182/blood-2013-08-521229
[66]	Shi B, Li J, Shi X, et al. (2017) TALEN-mediated knockout of CCR5 confers protection against infection of human immunodeficiency virus. J AIDS 74.
[67]	Tebas P, Stein D, Tang WW, et al. (2014) Gene editing of CCR5 in autologous CD4 T cells of persons infected with HIV. N Engl J Med 370: 901–910. doi: 10.1056/NEJMoa1300662
[68]	Mealer DA, Brennan AL, Jiang S, et al. (2013) Efficient clinical scale gene modification via zinc finger nuclease-targeted disruption of the HIV co-receptor CCR5. Hum Gene Ther 24: 245–258. doi: 10.1089/hum.2012.172
[69]	Strong CL, Guerra HP, Mathew KR, et al. (2015) Damaging the integrated HIV proviral DNA with TALENs. PLoS One 10: e0125652. doi: 10.1371/journal.pone.0125652
[70]	Horvath P, Barrangou R (2010) CRISPR/Cas, the immune system of bacteria and archaea. Science 327: 167–170. doi: 10.1126/science.1179555
[71]	Cong L, Ran FA, Cox D, et al. (2013) Multiplex genome engineering using CRISP/Cas systems. Science 339: 819–823. doi: 10.1126/science.1231143
[72]	Hsu PD, Lander ES, Zhang F (2014) Development and applications of CRISPR-Case9 for genome engineering. Cell 157: 1262–1278. doi: 10.1016/j.cell.2014.05.010
[73]	Ebina H, Misawa N, Kanemura Y, et al. (2013) Harnessing the CRIPSR/Cas 9 system to disrupt latent HIV-1 provirus. Sci Rep 3: 2510. doi: 10.1038/srep02510
[74]	Hou P, Chen S, Wang S, et al. (2015) Genome editing of CXCR4 by CRISPR/Cas9 confers cells resistant to HIV-1 infection. Sci Rep 5: 15577. doi: 10.1038/srep15577
[75]	Ye L, Wang J, Beyer AI, et al. (2014) Seamless modification of wild-type induced pluripotent stem cells to the natural CCR5Delta32 mutation confers resistance to HIV infection. PNAS 111: 9591–9596. doi: 10.1073/pnas.1407473111
[76]	Dampier W, Nonnemacher MR, Sullivan NT, et al. (2014) HIV excision utilizing CRISPR/Cas 9 technology: attacking the proviral quasispecies in reservoirs to achieve a cure. MOJ Immunol 1: 00022.
[77]	Zhu W, Lei R, De Duff Y, et al. (2015) The CRISPR/Cas9 system inactivates latent HIV-1 proviral DNA. Retrovirology 12: 22. doi: 10.1186/s12977-015-0150-z
[78]	Wang Z, Pan Q, Gendron P, et al. (2016) CRISPR/Cas-9-derived mutations both inhibit HIV-1 replication and accelerate viral escape. Cell Rep 15: 481–489. doi: 10.1016/j.celrep.2016.03.042

Reader Comments

Your name:*

Email:*
© 2018 the Author(s), licensee AIMS Press. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0)