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The Antiviral Immune Response and Its Impact on the HIV-1 Reservoir

  • Rebecca T. Veenhuis
  • Joel N. Blankson
Chapter
Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 417)

Abstract

Latently infected resting memory CD4+ T cells represent a major barrier to HIV-1 eradication. Studies have shown that it will not be possible to cure HIV-1 infection unless these cells are eliminated. Latently infected cells probably do not express viral antigens and thus may not be susceptible to the HIV-1 specific immune response, nevertheless the size and composition of the reservoir is influenced by the immune system. In this chapter, we review the different components of the HIV-1 specific immune response and discuss how the immune system can be harnessed to eradicate the virus.

References

  1. Ackerman ME, Mikhailova A, Brown EP, Dowell KG, Walker BD, Bailey-Kellogg C, Suscovich TJ, Alter G (2016) Polyfunctional HIV-1-specific antibody responses are associated with spontaneous HIV-1 control. PLoS Pathog 12(1):e1005315PubMedPubMedCentralGoogle Scholar
  2. Almeida JR, Price DA, Papagno L, Arkoub ZA, Sauce D, Bornstein E, Asher TE, Samri A, Schnuriger A, Theodorou I, Costagliola D, Rouzioux C, Agut H, Marcelin AG, Douek D, Autran B, Appay V (2007) Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 204(10):2473–2485PubMedPubMedCentralGoogle Scholar
  3. Altfeld M, Gale M Jr (2015) Innate immunity against HIV-1 infection. Nat Immunol 16(6):554–562Google Scholar
  4. Altfeld M, Addo MM, Rosenberg ES, Hecht FM, Lee PK, Vogel M, Yu XG, Draenert R, Johnston MN, Strick D, Allen TM, Feeney ME, Kahn JO, Sekaly RP, Levy JA, Rockstroh JK, Goulder PJ, Walker BD (2003) Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection. AIDS (London, England) 17(18):2581–2591PubMedGoogle Scholar
  5. Altman JD, Moss PA, Goulder PJ, Barouch DH, McHeyzer-Williams MG, Bell JI, McMichael AJ, Davis MM.2011 (1996) Phenotypic analysis of antigen-specific T lymphocytes. Science 274:94–96, J Immunol (Baltimore, Md.: 1950) 187(1):7–9PubMedGoogle Scholar
  6. Alvarez RA, Hamlin RE, Monroe A, Moldt B, Hotta MT, Rodriguez Caprio G, Fierer DS, Simon V, Chen BK (2014) HIV-1 Vpu antagonism of tetherin inhibits antibody-dependent cellular cytotoxic responses by natural killer cells. J Virol 88(11):6031–6046PubMedPubMedCentralGoogle Scholar
  7. Andres C, Plana M, Guardo AC, Alvarez-Fernandez C, Climent N, Gallart T, Leon A, Clotet B, Autran B, Chomont N, Gatell JM, Sanchez-Palomino S, Garcia F (2015) HIV-1 reservoir dynamics after vaccination and antiretroviral therapy interruption are associated with dendritic cell vaccine-induced T cell responses. J Virol 89(18):9189–9199PubMedPubMedCentralGoogle Scholar
  8. Asmuth DM, Murphy RL, Rosenkranz SL, Lertora JJL, Kottilil S, Cramer Y, Chan ES, Schooley RT, Rinaldo CR, Thielman N, Li XD, Wahl SM, Shore J, Janik J, Lempicki RA, Simpson Y, Pollard RB & for the ACTG A5192 Team (2010) Safety, tolerability and mechanisms of antiretroviral activity of peginterferon alfa-2a in HIV-1-mono-infected subjects: a phase II clinical trial. J Infect Dis 201(11):1686–1696PubMedPubMedCentralGoogle Scholar
  9. Azzoni L, Foulkes AS, Papasavvas E, Mexas AM, Lynn KM, Mounzer K, Tebas P, Jacobson JM, Frank I, Busch MP, Deeks SG, Carrington M, O’Doherty U, Kostman J, Montaner LJ (2013) Pegylated interferon Alfa-2a monotherapy results in suppression of HIV-1 type 1 replication and decreased cell-associated HIV-1 DNA integration. J Infect Dis 207(2):213–222PubMedPubMedCentralGoogle Scholar
  10. Bailey JR, Williams TM, Siliciano RF, Blankson JN (2006) Maintenance of viral suppression in HIV-1-infected HLA-B*57 + elite suppressors despite CTL escape mutations. J Exp Med 203(5):1357–1369PubMedPubMedCentralGoogle Scholar
  11. Bar KJ, Sneller MC, Harrison LJ, Justement JS, Overton ET, Petrone ME, Salantes DB, Seamon CA, Scheinfeld B, Kwan RW, Learn GH, Proschan MA, Kreider EF, Blazkova J, Bardsley M, Refsland EW, Messer M, Clarridge KE, Tustin NB, Madden PJ, Oden K, O’Dell SJ, Jarocki B, Shiakolas AR, Tressler RL, Doria-Rose NA, Bailer RT, Ledgerwood JE, Capparelli EV, Lynch RM, Graham BS, Moir S, Koup RA, Mascola JR, Hoxie JA, Fauci AS, Tebas P, Chun TW (2016) Effect of HIV-1 antibody VRC01 on viral rebound after treatment interruption. N Engl J Med 375(21):2037–2050PubMedPubMedCentralGoogle Scholar
  12. Barouch DH, Whitney JB, Moldt B, Klein F, Oliveira TY, Liu J, Stephenson KE, Chang HW, Shekhar K, Gupta S, Nkolola JP, Seaman MS, Smith KM, Borducchi EN, Cabral C, Smith JY, Blackmore S, Sanisetty S, Perry JR, Beck M, Lewis MG, Rinaldi W, Chakraborty AK, Poignard P, Nussenzweig MC, Burton DR (2013) Therapeutic efficacy of potent neutralizing HIV-1-specific monoclonal antibodies in SHIV-1-infected rhesus monkeys. Nature 503(7475):224–228PubMedPubMedCentralGoogle Scholar
  13. Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, Abraham J, Lederman MM, Benito JM, Goepfert PA, Connors M, Roederer M, Koup RA (2006) HIV-1 nonprogressors preferentially maintain highly functional HIV-1-specific CD8+ T cells. Blood 107(12):4781–4789PubMedPubMedCentralGoogle Scholar
  14. Blankson JN (2006) Viral reservoirs and HIV-1-specific immunity. Curr Opin HIV-1 AIDS 1(2):147–151Google Scholar
  15. Blankson JN, Bailey JR, Thayil S, Yang HC, Lassen K, Lai J, Gandhi SK, Siliciano JD, Williams TM, Siliciano RF (2007) Isolation and characterization of replication-competent human immunodeficiency virus type 1 from a subset of elite suppressors. J Virol 81(5):2508–2518PubMedGoogle Scholar
  16. Boasso A, Shearer GM (2008) Chronic innate immune activation as a cause of HIV-1 immunopathogenesis. Clin Immunol (Orlando, Fla.) 126(3):235–242PubMedGoogle Scholar
  17. Bonilla FA, Oettgen HC (2010) Adaptive immunity. J Allergy Clin Immunol 125(2 Suppl 2):S33–S40PubMedGoogle Scholar
  18. Borducchi EN, Cabral C, Stephenson KE, Liu J, Abbink P, Ng’ang’a D, Nkolola JP, Brinkman AL, Peter L, Lee BC, Jimenez J, Jetton D, Mondesir J, Mojta S, Chandrashekar A, Molloy K, Alter G, Gerold JM, Hill AL, Lewis MG, Pau MG, Schuitemaker H, Hesselgesser J, Geleziunas R, Kim JH, Robb ML, Michael NL, Barouch DH (2016) Ad26/MVA therapeutic vaccination with TLR7 stimulation in SIV-infected rhesus monkeys. Nature 540(7632):284–287PubMedPubMedCentralGoogle Scholar
  19. Borrow P, Lewicki H, Hahn BH, Shaw GM, Oldstone MB (1994) Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection. J Virol 68(9):6103–6110PubMedPubMedCentralGoogle Scholar
  20. Boue F, Reynes J, Rouzioux C, Emilie D, Souala F, Tubiana R, Goujard C, Lancar R, Costagliola D (2011) Alpha interferon administration during structured interruptions of combination antiretroviral therapy in patients with chronic HIV-1 infection: INTERVAC ANRS 105 trial. AIDS (London, England) 25(1):115–118PubMedGoogle Scholar
  21. Boulet S, Kleyman M, Kim JY, Kamya P, Sharafi S, Simic N, Bruneau J, Routy JP, Tsoukas CM, Bernard NF (2008a) A combined genotype of KIR3DL1 high expressing alleles and HLA-B*57 is associated with a reduced risk of HIV-1 infection. AIDS (London, England) 22(12):1487–1491Google Scholar
  22. Boulet S, Sharafi S, Simic N, Bruneau J, Routy JP, Tsoukas CM, Bernard NF (2008b) Increased proportion of KIR3DS1 homozygotes in HIV-1-exposed uninfected individuals. AIDS (London, England) 22(5):595–599PubMedGoogle Scholar
  23. Bruner KM, Murray AJ, Pollack RA, Soliman MG, Laskey SB, Capoferri AA, Lai J, Strain MC, Lada SM, Hoh R, Ho YC, Richman DD, Deeks SG, Siliciano JD, Siliciano RF (2016) Defective proviruses rapidly accumulate during acute HIV-1 infection. Nat Med 22(9):1043–1049PubMedPubMedCentralGoogle Scholar
  24. Buckheit RW 3rd, Salgado M, Martins KO, Blankson JN (2013a) The implications of viral reservoirs on the elite control of HIV-1 infection. Cell Mol Life Sci: CMLS 70(6):1009–1019PubMedGoogle Scholar
  25. Buckheit RW, Siliciano RF, Blankson JN (2013b) Primary CD8(+) T cells from elite suppressors effectively eliminate non-productively HIV-1 infected resting and activated CD4(+) T cells. Retrovirology 10(1):68PubMedPubMedCentralGoogle Scholar
  26. Cartwright EK, Spicer L, Smith SA, Lee D, Fast R, Paganini S, Lawson BO, Nega M, Easley K, Schmitz JE, Bosinger SE, Paiardini M, Chahroudi A, Vanderford TH, Estes JD, Lifson JD, Derdeyn CA, Silvestri G (2016) CD8(+) lymphocytes are required for maintaining viral suppression in SIV-infected macaques treated with short-term antiretroviral therapy. Immunity 20;45(3):656–668PubMedPubMedCentralGoogle Scholar
  27. Caskey M, Klein F, Nussenzweig MC (2016) Broadly neutralizing antibodies for HIV-1 prevention or immunotherapy. N Engl J Med 375(21):2019–2021PubMedGoogle Scholar
  28. Catano G, Kulkarni H, He W, Marconi VC, Agan BK, Landrum M, Anderson S, Delmar J, Telles V, Song L, Castiblanco J, Clark RA, Dolan MJ, Ahuja SK (2008) HIV-1 disease-influencing effects associated with ZNRD1, HCP5 and HLA-C alleles are attributable mainly to either HLA-A10 or HLA-B*57 alleles. PLoS ONE 3(11):e3636PubMedPubMedCentralGoogle Scholar
  29. Chan AC, Carter PJ (2010) Therapeutic antibodies for autoimmunity and inflammation. Nat Rev Immunol 10(5):301–316PubMedGoogle Scholar
  30. Chehimi J, Papasavvas E, Tomescu C, Gekonge B, Abdulhaqq S, Raymond A, Hancock A, Vinekar K, Carty C, Reynolds G, Pistilli M, Mounzer K, Kostman J, Montaner LJ (2010) Inability of plasmacytoid dendritic cells to directly lyse HIV-1-Infected autologous CD4(+) T cells despite induction of tumor necrosis factor-related apoptosis-inducing ligand. J Virol 84(6):2762–2773PubMedGoogle Scholar
  31. Cheng L, Ma J, Li J, Li D, Li G, Li F, Zhang Q, Yu H, Yasui F, Ye C, Tsao LC, Hu Z, Su L, Zhang L (2017) Blocking type I interferon signaling enhances T cell recovery and reduces HIV-1 reservoirs. J Clin Investig 127(1):269–279PubMedGoogle Scholar
  32. Cohen GB, Gandhi RT, Davis DM, Mandelboim O, Chen BK, Strominger JL, Baltimore D (1999) The selective downregulation of class I major histocompatibility complex proteins by HIV-1 protects HIV-1-infected cells from NK cells. Immunity 10(6):661–671PubMedGoogle Scholar
  33. Collins KL, Chen BK, Kalams SA, Walker BD, Baltimore D (1998) HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 391(6665):397–401PubMedGoogle Scholar
  34. Connick E, Mattila T, Folkvord JM, Schlichtemeier R, Meditz AL, Ray MG, McCarter MD, Mawhinney S, Hage A, White C, Skinner PJ (2007) CTL fail to accumulate at sites of HIV-1 replication in lymphoid tissue. J Immunol (Baltimore, Md.: 1950) 178(11):6975–6983PubMedGoogle Scholar
  35. Dalmasso C, Carpentier W, Meyer L, Rouzioux C, Goujard C, Chaix ML, Lambotte O, Avettand-Fenoel V, Le Clerc S, de Senneville LD, Deveau C, Boufassa F, Debre P, Delfraissy JF, Broet P, Theodorou I, ANRS Genome Wide Association 01 (2008) Distinct genetic loci control plasma HIV-1-RNA and cellular HIV-1-DNA levels in HIV-1 infection: the ANRS genome wide association 01 study. PloS one 3(12):e3907PubMedPubMedCentralGoogle Scholar
  36. Deng K, Pertea M, Rongvaux A, Wang L, Durand CM, Ghiaur G, Lai J, McHugh HL, Hao H, Zhang H, Margolick JB, Gurer C, Murphy AJ, Valenzuela DM, Yancopoulos GD, Deeks SG, Strowig T, Kumar P, Siliciano JD, Salzberg SL, Flavell RA, Shan L, Siliciano RF (2015) Broad CTL response is required to clear latent HIV-1 due to dominance of escape mutations. Nature 517(7534):381–385PubMedPubMedCentralGoogle Scholar
  37. Denton PW, Long JM, Wietgrefe SW, Sykes C, Spagnuolo RA, Snyder OD, Perkey K, Archin NM, Choudhary SK, Yang K, Hudgens MG, Pastan I, Haase AT, Kashuba AD, Berger EA, Margolis DM, Garcia JV (2014) Targeted cytotoxic therapy kills persisting hiv-1 infected cells during ART. PLoS Pathog 10(1):e1003872. doi:10.1371/journal.ppat.1003872CrossRefPubMedPubMedCentralGoogle Scholar
  38. Dianzani F, Rozera G, Abbate I, D’Offizi G, Abdeddaim A, Vlassi C, Antonucci G, Narciso P, Martini F, Capobianchi MR (2008) Interferon may prev HIV-1 viral rebound after HAART interruption in HIV-1 patients. J Interferon cytokine Res: Off J Int Interferon Cytokine Res 28(1):1–3Google Scholar
  39. Doyle T, Goujon C, Malim MH (2015) HIV-1 and interferons: who’s interfering with whom? Nat Rev Microbiol 13(7):403–413PubMedGoogle Scholar
  40. Emu B, Sinclair E, Hatano H, Ferre A, Shacklett B, Martin JN, McCune JM, Deeks SG (2008) HLA class I-restricted T-cell responses may contribute to the control of human immunodeficiency virus infection, but such responses are not always necessary for long-term virus control. J Virol 82(11):5398–5407PubMedPubMedCentralGoogle Scholar
  41. Euler Z, Alter G (2015) Exploring the potential of monoclonal antibody therapeutics for HIV-1 eradication. AIDS Res Hum Retroviruses 31(1):13–24PubMedPubMedCentralGoogle Scholar
  42. Fellay J, Shianna KV, Ge D, Colombo S, Ledergerber B, Weale M, Zhang K, Gumbs C, Castagna A, Cossarizza A, Cozzi-Lepri A, De Luca A, Easterbrook P, Francioli P, Mallal S, Martinez-Picado J, Miro JM, Obel N, Smith JP, Wyniger J, Descombes P, Antonarakis SE, Letvin NL, McMichael AJ, Haynes BF, Telenti A, Goldstein DB (2007) A whole-genome association study of major determinants for host control of HIV-1. Science (New York, N.Y.) 317(5840):944–947Google Scholar
  43. Ferre AL, Hunt PW, Critchfield JW, Young DH, Morris MM, Garcia JC, Pollard RB, Yee HF Jr, Martin JN, Deeks SG, Shacklett BL (2009) Mucosal immune responses to HIV-1 in elite controllers: a potential correlate of immune control. Blood 113(17):3978–3989PubMedPubMedCentralGoogle Scholar
  44. Folkvord JM, Armon C, Connick E (2005) Lymphoid follicles are sites of heightened human immunodeficiency virus type 1 (HIV-1) replication and reduced antiretroviral effector mechanisms. AIDS Res Hum Retroviruses 21(5):363–370Google Scholar
  45. Friedrich TC, Valentine LE, Yant LJ, Rakasz EG, Piaskowski SM, Furlott JR, Weisgrau KL, Burwitz B, May GE, Leon EJ, Soma T, Napoe G, Capuano SV 3rd, Wilson NA, Watkins DI (2007) Subdominant CD8+ T-cell responses are involved in durable control of AIDS virus replication. J Virol 81(7):3465–3476PubMedPubMedCentralGoogle Scholar
  46. Fukazawa Y, Lum R, Okoye AA, Park H, Matsuda K, Bae JY, Hagen SI, Shoemaker R, Deleage C, Lucero C, Morcock D, Swanson T, Legasse AW, Axthelm MK, Hesselgesser J, Geleziunas R, Hirsch VM, Edlefsen PT, Piatak M Jr, Estes JD, Lifson JD, Picker LJ (2015) B cell follicle sanctuary permits persistent productive simian immunodeficiency virus infection in elite controllers. Nat Med 21(2):132–139PubMedPubMedCentralGoogle Scholar
  47. GarcÃ-a F, Climent N, Assoumou L, Gil C, González N, AlcamÃ- J, LeÃ3n A, Romeu J, Dalmau J, MartÃ-nez-Picado J, Lifson J, Autran B, Costagliola D, Clotet B, Gatell JM, Plana M, Gallart T & for the DCV2/MANON07- AIDS Vaccine Research Objective Study Group (2011) A therapeutic dendritic cell-based vaccine for HIV-1 infection. J Infect Dis 203(4):473–478Google Scholar
  48. Goede V, Fischer K, Busch R, Engelke A, Eichhorst B, Wendtner CM, Chagorova T, de la Serna J, Dilhuydy MS, Illmer T, Opat S, Owen CJ, Samoylova O, Kreuzer KA, Stilgenbauer S, Dohner H, Langerak AW, Ritgen M, Kneba M, Asikanius E, Humphrey K, Wenger M, Hallek M (2014) Obinutuzumab plus chlorambucil in patients with CLL and coexisting conditions. N Engl J Med 370(12):1101–1110PubMedGoogle Scholar
  49. Goff SP (2003) Death by deamination: a novel host restriction system for HIV-1. Cell 114(3):281–283PubMedGoogle Scholar
  50. Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, Ganusov VV, Keele BF, Learn GH, Turnbull EL, Salazar MG, Weinhold KJ, Moore S, CHAVI Clinical Core B, Letvin N, Haynes BF, Cohen MS, Hraber P, Bhattacharya T, Borrow P, Perelson AS, Hahn BH, Shaw GM, Korber BT, McMichael AJ (2009) The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med 206(6):1253–1272PubMedPubMedCentralGoogle Scholar
  51. Gougeon ML (2003) Apoptosis as an HIV-1 strategy to escape immune attack. Nat Rev Immunol 3(5):392–404PubMedGoogle Scholar
  52. Goujard C, Chaix ML, Lambotte O, Deveau C, Sinet M, Guergnon J, Courgnaud V, Rouzioux C, Delfraissy JF, Venet A, Meyer L & Agence Nationale de Recherche sur le Sida PRIMO Study Group (2009) Spontaneous control of viral replication during primary HIV-1 infection: when is “HIV-1 controller” status established? Clin Infect Dis: Off Publ Infect Dis Soc Am 49(6):982–986Google Scholar
  53. Graf EH, Mexas AM, Yu JJ, Shaheen F, Liszewski MK, Di Mascio M, Migueles SA, Connors M, O’Doherty U (2011) Elite suppressors harbor low levels of integrated HIV-1 DNA and high levels of 2-LTR circular HIV-1 DNA compared to HIV-1+ patients on and off HAART. PLoS Pathog 7(2):e1001300PubMedPubMedCentralGoogle Scholar
  54. Graf EH, Pace MJ, Peterson BA, Lynch LJ, Chukwulebe SB, Mexas AM, Shaheen F, Martin JN, Deeks SG, Connors M, Migueles SA, O’Doherty U (2013) Gag-positive reservoir cells are susceptible to HIV-1-specific cytotoxic T lymphocyte mediated clearance in vitro and can be detected in vivo. PLoS ONE 8(8):e71879PubMedPubMedCentralGoogle Scholar
  55. Gulzar N, Copeland KF (2004) “CD8+ T-cells: function and response to HIV-1 infection”. Curr HIV-1 Res 2(1):23–37Google Scholar
  56. Halper-Stromberg A, Lu CL, Klein F, Horwitz JA, Bournazos S, Nogueira L, Eisenreich TR, Liu C, Gazumyan A, Schaefer U, Furze RC, Seaman MS, Prinjha R, Tarakhovsky A, Ravetch JV, Nussenzweig MC (2014) Broadly neutralizing antibodies and viral inducers decrease rebound from HIV-1 latent reservoirs in humanized mice. Cell 158(5):989–999PubMedPubMedCentralGoogle Scholar
  57. Han Y, Lai J, Barditch-Crovo P, Gallant JE, Williams TM, Siliciano, RF, Blankson JN (2008) The role of protective HCP5 and HLA-C associated polymorphisms in the control of HIV-1 replication in a subset of elite suppressors. AIDS (London, England) 22(4):541–544PubMedGoogle Scholar
  58. Hansen SG, Ford JC, Lewis MS, Ventura AB, Hughes CM, Coyne-Johnson L, Whizin N, Oswald K, Shoemaker R, Swanson T, Legasse AW, Chiuchiolo MJ, Parks CL, Axthelm MK, Nelson JA, Jarvis MA, Piatak M Jr, Lifson JD, Picker LJ (2011) Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine. Nature 473(7348):523–527PubMedPubMedCentralGoogle Scholar
  59. Hansen SG, Sacha JB, Hughes CM, Ford JC, Burwitz BJ, Scholz I, Gilbride RM, Lewis MS, Gilliam AN, Ventura AB, Malouli D, Xu G, Richards R, Whizin N, Reed JS, Hammond KB, Fischer M, Turner JM, Legasse AW, Axthelm MK, Edlefsen PT, Nelson JA, Lifson JD, Fruh K, Picker LJ (2013) Cytomegalovirus vectors violate CD8+ T cell epitope recognition paradigms. Science (New York, N.Y.) 340(6135):1237874Google Scholar
  60. Hansen SG, Wu HL, Burwitz BJ, Hughes CM, Hammond KB, Ventura AB, Reed JS, Gilbride RM, Ainslie E, Morrow DW, Ford JC, Selseth AN, Pathak R, Malouli D, Legasse AW, Axthelm MK, Nelson JA, Gillespie GM, Walters LC, Brackenridge S, Sharpe HR, Lopez CA, Fruh K, Korber BT, McMichael AJ, Gnanakaran S, Sacha JB, Picker LJ (2016) Broadly targeted CD8(+) T cell responses restricted by major histocompatibility complex E. Science (New York, N.Y.) 351(6274):714–720Google Scholar
  61. Hardy GAD, Sieg S, Rodriguez B, Anthony D, Asaad R, Jiang W, Mudd J, Schacker T, Funderburg N.T, Pilch-Cooper HA, Debernardo R, Rabin RL, Lederman MM & Harding CV (2013) Interferon-α the primary plasma type-I IFN in HIV-1 infection and correlates with immune activation and disease markers. PLoS ONE 8(2):e56527. doi:10.1371/journal.pone.0056527CrossRefGoogle Scholar
  62. Harris RS, Bishop KN, Sheehy AM, Craig HM, Petersen-Mahrt SK, Watt IN, Neuberger MS, Malim MH (2003) DNA deamination mediates innate immunity to retroviral infection. Cell 113(6):803–809PubMedGoogle Scholar
  63. Haynes BF, Gilbert PB, McElrath MJ, Zolla-Pazner S, Tomaras GD, Alam SM, Evans DT, Montefiori DC, Karnasuta C, Sutthent R, Liao HX, DeVico AL, Lewis GK, Williams C, Pinter A, Fong Y, Janes H, DeCamp A, Huang Y, Rao M, Billings E, Karasavvas N, Robb ML, Ngauy V, de Souza MS, Paris R, Ferrari G, Bailer RT, Soderberg KA, Andrews C, Berman PW, Frahm N, De Rosa SC, Alpert MD, Yates NL, Shen X, Koup RA, Pitisuttithum P, Kaewkungwal J, Nitayaphan S, Rerks-Ngarm S, Michael NL, Kim JH (2012) Immune-correlates analysis of an HIV-1 vaccine efficacy trial. N Engl J Med 366(14):1275–1286PubMedPubMedCentralGoogle Scholar
  64. Hersperger AR, Pereyra F, Nason M, Demers K, Sheth P, Shin LY, Kovacs CM, Rodriguez B, Sieg SF, Teixeira-Johnson L, Gudonis D, Goepfert PA, Lederman MM, Frank I, Makedonas G, Kaul R, Walker BD, Betts MR (2010) Perforin expression directly ex vivo by HIV-1-specific CD8 T-cells is a correlate of HIV-1 elite control. PLoS Pathog 6(5):e1000917PubMedPubMedCentralGoogle Scholar
  65. Ho YC, Shan L, Hosmane NN, Wang J, Laskey SB, Rosenbloom DI, Lai J, Blankson JN, Siliciano JD, Siliciano RF (2013) Replication-competent noninduced proviruses in the latent reservoir increase barrier to HIV-1 cure. Cell 155(3):540–551PubMedPubMedCentralGoogle Scholar
  66. Horwitz JA, Halper-Stromberg A, Mouquet H, Gitlin AD, Tretiakova A, Eisenreich TR, Malbec M, Gravemann S, Billerbeck E, Dorner M, Buning H, Schwartz O, Knops E, Kaiser R, Seaman MS, Wilson JM, Rice CM, Ploss A, Bjorkman PJ, Klein F, Nussenzweig MC (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(41):16538–16543PubMedGoogle Scholar
  67. International HIV-1 Controllers Study, Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PI, Walker BD, Ripke S, Brumme CJ, Pulit SL, Carrington M, Kadie CM, Carlson JM, Heckerman D, Graham RR, Plenge RM, Deeks SG, Gianniny L, Crawford G, Sullivan J, Gonzalez E, Davies L, Camargo A, Moore JM, Beattie N, Gupta S, Crenshaw A, Burtt NP, Guiducci C, Gupta N, Gao X, Qi Y, Yuki Y, Piechocka-Trocha A, Cutrell E, Rosenberg R, Moss KL, Lemay P, O’Leary J, Schaefer T, Verma P, Toth I, Block B, Baker B, Rothchild A, Lian J, Proudfoot J, Alvino D.M, Vine S, Addo MM, Allen TM, Altfeld M, Henn MR, Le Gall S, Streeck H, Haas DW, Kuritzkes DR, Robbins GK, Shafer RW, Gulick RM, Shikuma CM, Haubrich R, Riddler S, Sax PE, Daar ES, Ribaudo HJ, Agan B, Agarwal S, Ahern RL, Allen BL, Altidor S, Altschuler EL, Ambardar S, Anastos K, Anderson B, Anderson V, Andrady U, Antoniskis D, Bangsberg D, Barbaro D, Barrie W, Bartczak J, Barton S, Basden P, Basgoz N, Bazner S, Bellos NC, Benson AM, Berger J, Bernard NF, Bernard AM, Birch C, Bodner SJ, Bolan RK, Boudreaux ET, Bradley M, Braun JF, Brndjar JE, Brown SJ, Brown K, Brown ST, Burack J, Bush LM, Cafaro V, Campbell O, Campbell J, Carlson RH, Carmichael JK, Casey KK, Cavacuiti C, Celestin G, Chambers ST, Chez N, Chirch LM, Cimoch PJ, Cohen D, Cohn LE, Conway B, Cooper DA, Cornelson B, Cox DT, Cristofano MV, Cuchural G Jr, Czartoski JL, Dahman JM, Daly JS, Davis BT, Davis K, Davod SM, DeJesus E, Dietz CA, Dunham E, Dunn ME, Ellerin TB, Eron JJ, Fangman JJ, Farel CE, Ferlazzo H, Fidler S, Fleenor-Ford A, Frankel R, Freedberg KA, French NK, Fuchs JD, Fuller JD, Gaberman J, Gallant JE, Gandhi RT, Garcia E, Garmon D, Gathe JC Jr, Gaultier, CR, Gebre W, Gilman FD, Gilson I, Goepfert P, Gottlieb MS, Goulston C, Groger RK, Gurley TD, Haber S, Hardwicke R, Hardy WD, Harrigan PR, Hawkins, TN, Heath S, Hecht FM, Henry WK, Hladek M, Hoffman RP, Horton JM, Hsu RK, Huhn GD, Hunt P, Hupert MJ, Illeman ML, Jaeger H, Jellinger RM, John M, Johnson JA, Johnson KL, Johnson H, Johnson K, Joly J, Jordan WC, Kauffman CA, Khanlou H, Killian RK, Kim AY, Kim DD, Kinder CA, Kirchner JT, Kogelman L, Kojic EM, Korthuis PT, Kurisu W, Kwon DS, LaMar M, Lampiris H, Lanzafame M, Lederman MM, Lee DM, Lee JM, Lee MJ, Lee ET, Lemoine J, Levy JA, Llibre JM, Liguori MA, Little SJ, Liu AY, Lopez AJ, Loutfy MR, Loy D, Mohammed DY, Man A, Mansour MK, Marconi VC, Markowitz M, Marques R, Martin JN, Martin HL Jr, Mayer KH, McElrath MJ, McGhee TA, McGovern BH, McGowan K, McIntyre D, Mcleod GX, Menezes P, Mesa G, Metroka CE, Meyer-Olson D, Miller AO, Montgomery K, Mounzer KC, Nagami EH, Nagin I, Nahass RG, Nelson MO, Nielsen C, Norene DL, O’Connor DH, Ojikutu BO, Okulicz J, Oladehin OO, Oldfield EC 3rd, Olender SA, Ostrowski M, Owen WF Jr, Pae E, Parsonnet J, Pavlatos AM, Perlmutter AM, Pierce MN, Pincus JM, Pisani L, Price LJ, Proia L, Prokesch RC, Pujet HC, Ramgopal M, Rathod A, Rausch M, Ravishankar J, Rhame FS, Richards CS, Richman DD, Rodes B, Rodriguez M, Rose RC 3rd, Rosenberg ES, Rosenthal D, Ross PE, Rubin DS, Rumbaugh E, Saenz L, Salvaggio MR, Sanchez WC, Sanjana VM, Santiago S, Schmidt W, Schuitemaker H, Sestak PM, Shalit P, Shay W, Shirvani VN, Silebi VI, Sizemore JM Jr, Skolnik PR, Sokol-Anderson M, Sosman JM, Stabile P, Stapleton JT, Starrett S, Stein F, Stellbrink HJ, Sterman FL, Stone VE, Stone DR, Tambussi G, Taplitz RA, Tedaldi EM, Telenti A, Theisen W, Torres R, Tosiello L, Tremblay C, Tribble MA, Trinh PD, Tsao A, Ueda P, Vaccaro A, Valadas E, Vanig TJ, Vecino I, Vega VM, Veikley W, Wade BH, Walworth C, Wanidworanun C, Ward DJ, Warner DA, Weber RD, Webster D, Weis S, Wheeler DA, White DJ, Wilkins E, Winston A, Wlodaver CG, van’t Wout A, Wright DP, Yang OO, Yurdin DL, Zabukovic BW, Zachary KC, Zeeman B, Zhao M (2010) The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science (New York, N.Y.) 330(6010):1551–1557Google Scholar
  68. Isitman G, Lisovsky I, Tremblay-McLean A, Kovacs C, Harris M, Routy JP, Bruneau J, Wainberg MA, Tremblay C, Bernard NF (2016) Antibody-dependent cellular cytotoxicity activity of effector cells from HIV-1-infected elite and viral controllers. AIDS Res Hum Retroviruses 32(10–11):1079–1088PubMedGoogle Scholar
  69. Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, Blanchard J, Irwin CE, Safrit JT, Mittler J, Weinberger L, Kostrikis LG, Zhang L, Perelson AS, Ho DD (1999) Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med 189(6):991–998PubMedPubMedCentralGoogle Scholar
  70. Jones RB, O’Connor R, Mueller S, Foley M, Szeto GL, Karel D, Lichterfeld M, Kovacs C, Ostrowski MA, Trocha A, Irvine DJ, Walker BD (2014) Histone deacetylase inhibitors impair the elimination of HIV-1-infected cells by cytotoxic T-lymphocytes. PLoS Pathog 10(8):e1004287PubMedPubMedCentralGoogle Scholar
  71. Jones RB, Mueller S, O’Connor R, Rimpel K, Sloan DD, Karel D, Wong HC, Jeng EK, Thomas AS, Whitney JB, Lim SY, Kovacs C, Benko E, Karandish S, Huang SH, Buzon MJ, Lichterfeld M, Irrinki A, Murry JP, Tsai A, Yu H, Geleziunas R, Trocha A, Ostrowski MA, Irvine DJ, Walker BD (2016) A subset of latency-reversing agents expose HIV-1-infected resting CD4+ T-cells to recognition by cytotoxic T-lymphocytes. PLoS Pathog 12(4):e1005545PubMedPubMedCentralGoogle Scholar
  72. Julg B, Pereyra F, Buzon MJ, Piechocka-Trocha A, Clark MJ, Baker BM, Lian J, Miura T, Martinez-Picado J, Addo MM, Walker BD (2010) Infrequent recovery of HIV-1 from but robust exogenous infection of activated CD4(+) T cells in HIV-1 elite controllers. Clin Infect Dis: Off Publ Infect Dis Soc Am 51(2):233–238Google Scholar
  73. Keele BF, Giorgi EE, Salazar-Gonzalez JF, Decker JM, Pham KT, Salazar MG, Sun C, Grayson T, Wang S, Li H, Wei X, Jiang C, Kirchherr JL, Gao F, Anderson JA, Ping LH, Swanstrom R, Tomaras GD, Blattner WA, Goepfert PA, Kilby JM, Saag MS, Delwart EL, Busch MP, Cohen MS, Montefiori DC, Haynes BF, Gaschen B, Athreya GS, Lee HY, Wood N, Seoighe C, Perelson AS, Bhattacharya T, Korber BT, Hahn BH, Shaw GM (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci USA 105(21):7552–7557PubMedGoogle Scholar
  74. Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, Astemborski J, Cheng J, Goedert JJ, Vlahov D, Hilgartner M, Cox S, Little AM, Alexander GJ, Cramp ME, O’Brien SJ, Rosenberg WM, Thomas DL, Carrington M (2004) HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science (New York, N.Y.) 305(5685):872–874Google Scholar
  75. Kieffer TL, Kwon P, Nettles RE, Han Y, Ray SC, Siliciano RF (2005) G→ A hypermutation in protease and reverse transcriptase regions of human immunodeficiency virus type 1 residing in resting CD4+ T cells in vivo. J Virol 79(3):1975–1980PubMedPubMedCentralGoogle Scholar
  76. Klein F, Halper-Stromberg A, Horwitz JA, Gruell H, Scheid JF, Bournazos S, Mouquet H, Spatz LA, Diskin R, Abadir A, Zang T, Dorner M, Billerbeck E, Labitt RN, Gaebler C, Marcovecchio PM, Incesu RB, Eisenreich TR, Bieniasz PD, Seaman MS, Bjorkman PJ, Ravetch JV, Ploss A, Nussenzweig MC (2012) HIV-1 therapy by a combination of broadly neutralizing antibodies in humanized mice. Nature 492(7427):118–122PubMedGoogle Scholar
  77. Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, Borkowsky W, Farthing C, Ho DD (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68(7):4650–4655PubMedPubMedCentralGoogle Scholar
  78. Lambotte O, Boufassa F, Madec Y, Nguyen A, Goujard C, Meyer L, Rouzioux C, Venet A, Delfraissy JF & SEROCO-HEMOCO Study Group (2005) HIV-1 controllers: a homogeneous group of HIV-1-infected patients with spontaneous control of viral replication. Clin infect dis: off publ Infect Dis Soc Am 41(7):1053–1056Google Scholar
  79. Lambotte O, Ferrari G, Moog C, Yates NL, Liao HX, Parks RJ, Hicks CB, Owzar K, Tomaras GD, Montefiori DC, Haynes BF, Delfraissy JF (2009) Heterogeneous neutralizing antibody and antibody-dependent cell cytotoxicity responses in HIV-1 elite controllers. AIDS (London, England) 23(8):897–906PubMedPubMedCentralGoogle Scholar
  80. Lane HC, Kovacs JA, Feinberg J, Herpin B, Davey V, Walker R, Deyton L, Metcalf JA, Baseler M, Salzman N (1988) Anti-retroviral effects of interferon-alpha in AIDS-associated Kaposi’s sarcoma. Lancet (London, England) 2(8622):1218–1222Google Scholar
  81. Lavender KJ, Gibbert K, Peterson KE, Van Dis E, Francois S, Woods T, Messer RJ, Gawanbacht A, Müller JA, Müller J, Phillips K, Race B, Harper MS, Guo K, Lee EJ, Trilling M, Hengel H, Piehler J, Verheyen J, Wilson CC, Santiago ML, Hasenkrug KJ, Dittmer U (2016) Interferon alpha subtype-specific suppression of HIV-1 infection in vivo. J Virol 90(13):6001–6013PubMedPubMedCentralGoogle Scholar
  82. Lecossier D, Bouchonnet F, Clavel F, Hance AJ (2003) Hypermutation of HIV-1 DNA in the absence of the Vif protein. Science (New York, N.Y.) 300(5622):1112Google Scholar
  83. Li SX, Barrett BS, Heilman KJ, Messer RJ, Liberatore RA, Bieniasz PD, Kassiotis G, Hasenkrug KJ, Santiago ML (2014) Tetherin promotes the innate and adaptive cell-mediated immune response against retrovirus infection in vivo. J Immunol (Baltimore, MD: 1950) 193(1):306–316Google Scholar
  84. Limou S, Le Clerc S, Coulonges C, Carpentier W, Dina C, Delaneau O, Labib T, Taing L, Sladek R, Deveau C, Ratsimandresy R, Montes M, Spadoni JL, Lelievre JD, Levy Y, Therwath A, Schachter F, Matsuda F, Gut I, Froguel P, Delfraissy JF, Hercberg S, Zagury JF & ANRS Genomic Group (2009) Genomewide association study of an AIDS-nonprogression cohort emphasizes the role played by HLA genes (ANRS Genomewide Association Study 02). J Infect Dis 199(3):419–426Google Scholar
  85. Lynch RM, Boritz E, Coates EE, DeZure A, Madden P, Costner P, Enama ME, Plummer S, Holman L, Hendel CS, Gordon I, Casazza J, Conan-Cibotti M, Migueles SA, Tressler R, Bailer RT, McDermott A, Narpala S, O’Dell S, Wolf G, Lifson JD, Freemire BA, Gorelick RJ, Pandey JP, Mohan S, Chomont N, Fromentin R, Chun TW, Fauci AS, Schwartz RM, Koup RA, Douek DC, Hu Z, Capparelli E, Graham BS, Mascola JR, Ledgerwood JE, VRC 601 Study Team (2015) Virologic effects of broadly neutralizing antibody VRC01 administration during chronic HIV-1 infection. Sci Transl Med 7(319):319ra206Google Scholar
  86. Mangeat B, Turelli P, Caron G, Friedli M, Perrin L, Trono D (2003) Broad antiretroviral defence by human APOBEC3G through lethal editing of nascent reverse transcripts. Nature 424(6944):99–103PubMedGoogle Scholar
  87. Marras F, Nicco E, Bozzano F, Di Biagio A, Dentone C, Pontali E, Boni S, Setti M, Orofino G, Mantia E, Bartolacci V, Bisio F, Riva A, Biassoni R, Moretta L, De Maria A (2013) Natural killer cells in HIV-1 controller patients express an activated effector phenotype and do not up-regulate NKp44 on IL-2 stimulation. Proc Natl Acad Sci USA 110(29):11970–11975PubMedGoogle Scholar
  88. Martin MP, Gao X, Lee JH, Nelson GW, Detels R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, Trowsdale J, Wilson M, O’Brien SJ, Carrington M (2002) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 31(4):429–434PubMedGoogle Scholar
  89. Martin MP, Qi Y, Gao X, Yamada E, Martin JN, Pereyra F, Colombo S, Brown EE, Shupert WL, Phair J, Goedert JJ, Buchbinder S, Kirk GD, Telenti A, Connors M, O’Brien SJ, Walker BD, Parham P, Deeks SG, McVicar DW, Carrington M (2007) Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nat Genet 39(6):733–740PubMedPubMedCentralGoogle Scholar
  90. Migueles SA, Connors M (2015) Success and failure of the cellular immune response against HIV-1. Nat Immunol 16(6):563–570Google Scholar
  91. Migueles SA, Sabbaghian MS, Shupert WL, Bettinotti MP, Marincola FM, Martino L, Hallahan CW, Selig SM, Schwartz D, Sullivan J, Connors M (2000) HLA B*5701 is highly associated with restriction of virus replication in a subgroup of HIV-1-infected long term nonprogressors. Proc Natl Acad Sci USA 97(6):2709–2714PubMedGoogle Scholar
  92. Migueles SA, Laborico AC, Shupert WL, Sabbaghian MS, Rabin R, Hallahan CW, Van Baarle D, Kostense S, Miedema F, McLaughlin M, Ehler L, Metcalf J, Liu S, Connors M (2002) HIV-1-specific CD8+ T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol 3(11):1061–1068PubMedGoogle Scholar
  93. Migueles SA, Osborne CM, Royce C, Compton AA, Joshi RP, Weeks KA, Rood JE, Berkley AM, Sacha JB, Cogliano-Shutta NA, Lloyd M, Roby G, Kwan R, McLaughlin M, Stallings S, Rehm C, O’Shea MA, Mican J, Packard BZ, Komoriya A, Palmer S, Wiegand AP, Maldarelli F, Coffin JM, Mellors JW, Hallahan CW, Follman DA, Connors M (2008) Lytic granule loading of CD8+ T cells is required for HIV-1-infected cell elimination associated with immune control. Immunity 29(6):1009–1021PubMedPubMedCentralGoogle Scholar
  94. Norman JM, Mashiba M, McNamara LA, Onafuwa-Nuga A, Chiari-Fort E, Shen W, Collins KL (2011) The anti-viral factor APOBEC3G enhances natural killer cell recognition of HIV-1-infected primary T cells. Nat Immunol 12(10):975–983PubMedPubMedCentralGoogle Scholar
  95. O’Connell KA, Han Y, Williams TM, Siliciano RF, Blankson JN (2009) Role of natural killer cells in a cohort of elite suppressors: low frequency of the protective KIR3DS1 allele and limited inhibition of human immunodeficiency virus type 1 replication in vitro. J Virol 83(10):5028–5034PubMedPubMedCentralGoogle Scholar
  96. Okulicz JF, Lambotte O (2011) Epidemiology and clinical characteristics of elite controllers. Curr Opin HIV-1 AIDS 6(3):163–168PubMedGoogle Scholar
  97. Overbaugh J, Morris L (2012) The antibody response against HIV-1. Cold Spring Harb Perspect Med 2(1):a007039. doi:10.1101/cshperspect.a007039CrossRefPubMedPubMedCentralGoogle Scholar
  98. Pandrea I, Gaufin T, Gautam R, Kristoff J, Mandell D, Montefiori D, Keele BF, Ribeiro RM, Veazey RS, Apetrei C (2011) Functional cure of SIVagm infection in rhesus macaques results in complete recovery of CD4+ T cells and is reverted by CD8+ cell depletion. PLoS Pathog 7(8):e1002170PubMedPubMedCentralGoogle Scholar
  99. Pegu A, Asokan M, Wu L, Wang K, Hataye J, Casazza JP, Guo X, Shi W, Georgiev I, Zhou T, Chen X, O’Dell S, Todd JP, Kwong PD, Rao SS, Yang ZY, Koup RA, Mascola JR, Nabel GJ (2015) Activation and lysis of human CD4 cells latently infected with HIV-1. Nat commun 6:8447PubMedPubMedCentralGoogle Scholar
  100. Pereyra F, Addo MM, Kaufmann DE, Liu Y, Miura T, Rathod A, Baker B, Trocha A, Rosenberg R, Mackey E, Ueda P, Lu Z, Cohen D, Wrin T, Petropoulos CJ, Rosenberg ES, Walker BD (2008) Genetic and immunologic heterogeneity among persons who control HIV-1 infection in the absence of therapy. J Infect Dis 197(4):563–571PubMedGoogle Scholar
  101. Pham TN, Lukhele S, Hajjar F, Routy JP, Cohen EA (2014) HIV-1 Nef and Vpu protect HIV-1-infected CD4+ T cells from antibody-mediated cell lysis through down-modulation of CD4 and BST2. Retrovirology 11:15-4690-11-15PubMedPubMedCentralGoogle Scholar
  102. Phillips RE, Rowland-Jones S, Nixon DF, Gotch FM, Edwards JP, Ogunlesi AO, Elvin JG, Rothbard JA, Bangham CR, Rizza CR (1991) Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354(6353):453–459PubMedGoogle Scholar
  103. Picker LJ (2017) Therapeutic vaccination for HIV-1/SIV: what will it take for cure? In: Visions of HIV-1 Cure, Conference on Retroviruses and Opportunistic Infections (CROI), Seattle, WA, February 13–16, 2017Google Scholar
  104. Pollack RA, Jones RB, Pertea M, Bruner KM, Martin AR, Thomas AS, Capoferri AA, Beg SA, Huang SH, Karandish S, Hao H, Halper-Stromberg E, Yong PC, Kovacs C, Benko E, Siliciano RF, Ho YC (2017) Defective HIV-1 proviruses are expressed and can be recognized by cytotoxic T lymphocytes, which shape the proviral landscape. Cell host microbe 21(4):494–506.e4Google Scholar
  105. Richard J, Sindhu S, Pham TNQ, Belzile JP, Cohen à (2010) HIV-1 Vpr up-regulates expression of ligands for the activating NKG2D receptor and promotes NK cell–mediated killing. Blood 115(7):1354–1363PubMedGoogle Scholar
  106. Saez-Cirion A, Lacabaratz C, Lambotte O, Versmisse P, Urrutia A, Boufassa F, Barre-Sinoussi F, Delfraissy JF, Sinet M, Pancino G, Venet A & Agence Nationale de Recherches sur le Sida EP36 HIV-1 Controllers Study Group (2007) HIV-1 controllers exhibit potent CD8 T cell capacity to suppress HIV-1 infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci USA 104(16):6776–6781Google Scholar
  107. Saez-Cirion A, Sinet M, Shin SY, Urrutia A, Versmisse P, Lacabaratz C, Boufassa F, Avettand-Fenoel V, Rouzioux C, Delfraissy JF, Barre-Sinoussi F, Lambotte O, Venet A, Pancino G, ANRS EP36 HIV-1 Controllers Study Group (2009) Heterogeneity in HIV-1 suppression by CD8 T cells from HIV-1 controllers: association with Gag-specific CD8 T cell responses. J Immunol (Baltimore, MD: 1950) 182(12):7828–7837Google Scholar
  108. Sandler NG, Bosinger SE, Estes JD, Zhu RT, Tharp GK, Boritz E, Levin D, Wijeyesinghe S, Makamdop KN, del Prete GQ, Hill BJ, Timmer JK, Reiss E, Yarden G, Darko S, Contijoch E, Todd JP, Silvestri G, Nason M, Norgren RB Jr, Keele BF, Rao S, Langer JA, Lifson JD, Schreiber G, Douek DC (2014) Type I interferon responses in rhesus macaques prevent SIV infection and slow disease progression. Nature 511(7511):601–605PubMedPubMedCentralGoogle Scholar
  109. Scheid JF, Horwitz JA, Bar-On Y, Kreider EF, Lu CL, Lorenzi JCC, Feldmann A, Braunschweig M, Nogueira L, Oliveira T, Shimeliovich I, Patel R, Burke L, Cohen YZ, Hadrigan S, Settler A, Witmer-Pack M, West AP, Juelg B, Keler T, Hawthorne T, Zingman B, Gulick RM, Pfeifer N, Learn GH, Seaman MS, Bjorkman PJ, Klein F, Schlesinger SJ, Walker BD, Hahn BH, Nussenzweig MC, Caskey M (2016) HIV-1 antibody 3BNC117 suppresses viral rebound in humans during treatment interruption. Nature 535(7613):556–560PubMedPubMedCentralGoogle Scholar
  110. Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, Lifton MA, Racz P, Tenner-Racz K, Dalesandro M, Scallon BJ, Ghrayeb J, Forman MA, Montefiori DC, Rieber EP, Letvin NL, Reimann KA (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science (New York, N.Y.) 283(5403):857–860Google Scholar
  111. Scully E, Alter G (2016) NK Cells in HIV-1 Disease. Curr HIV-1/AIDS Rep 13:85–94Google Scholar
  112. Shah AH, Sowrirajan B, Davis ZB, Ward JP, Campbell EM, Planelles V, Barker E (2010) Degranulation of natural killer cells following interaction with HIV-1-infected cells is hindered by downmodulation of NTB-A by Vpu. Cell Host Microbe 8(5):397–409PubMedPubMedCentralGoogle Scholar
  113. Shan L, Deng K, Shroff NS, Durand CM, Rabi SA, Yang HC, Zhang H, Margolick JB, Blankson JN, Siliciano RF (2012) Stimulation of HIV-1-specific cytolytic T lymphocytes facilitates elimination of latent viral reservoir after virus reactivation. Immunity 36(3):491–501PubMedPubMedCentralGoogle Scholar
  114. Sheehy AM, Gaddis NC, Choi JD, Malim MH (2002) Isolation of a human gene that inhibits HIV-1 infection and is suppressed by the viral Vif protein. Nature 418(6898):646–650PubMedGoogle Scholar
  115. Shibata-Koyama M, Iida S, Misaka H, Mori K, Yano K, Shitara K, Satoh M (2009) Nonfucosylated rituximab potentiates human neutrophil phagocytosis through its high binding for FcgammaRIIIb and MHC class II expression on the phagocytotic neutrophils. Exp Hematol 37(3):309–321PubMedGoogle Scholar
  116. Shingai M, Nishimura Y, Klein F, Mouquet H, Donau OK, Plishka R, Buckler-White A, Seaman M, Piatak M Jr, Lifson JD, Dimitrov DS, Nussenzweig MC, Martin MA (2013) Antibody-mediated immunotherapy of macaques chronically infected with SHIV-1 suppresses viraemia. Nature 503(7475):277–280PubMedPubMedCentralGoogle Scholar
  117. Siliciano JD, Kajdas J, Finzi D, Quinn TC, Chadwick K, Margolick JB, Kovacs C, Gange SJ, Siliciano RF (2003) Long-term follow-up studies confirm the stability of the latent reservoir for HIV-1 in resting CD4+ T cells. Nat Med 9(6):727–728PubMedPubMedCentralGoogle Scholar
  118. Sloan DD, Lam CY, Irrinki A, Liu L, Tsai A, Pace CS, Kaur J, Murry JP, Balakrishnan M, Moore PA, Johnson S, Nordstrom JL, Cihlar T, Koenig S (2015) Targeting HIV-1 reservoir in infected CD4 T cells by dual-affinity re-targeting molecules (DARTs) that bind HIV-1 envelope and recruit cytotoxic T cells. PLoS Pathog 11(11):e1005233PubMedPubMedCentralGoogle Scholar
  119. Smalls-Mantey A, Doria-Rose N, Klein R, Patamawenu A, Migueles SA, Ko SY, Hallahan CW, Wong H, Liu B, You L, Scheid J, Kappes JC, Ochsenbauer C, Nabel GJ, Mascola JR, Connors M (2012) Antibody-dependent cellular cytotoxicity against primary HIV-1-infected CD4+ T cells is directly associated with the magnitude of surface IgG binding. J Virol 86(16):8672–8680PubMedPubMedCentralGoogle Scholar
  120. Specht A, DeGottardi MQ, Schindler M, Hahn B, Evans DT, Kirchhoff F (2008) Selective downmodulation of HLA-A and -B by Nef alleles from different groups of primate lentiviruses. Virology 373(1):229–237PubMedGoogle Scholar
  121. Sung JA, Pickeral J, Liu L, Stanfield-Oakley SA, Lam CY, Garrido C, Pollara J, LaBranche C, Bonsignori M, Moody MA, Yang Y, Parks R, Archin N, Allard B, Kirchherr J, Kuruc JD, Gay CL, Cohen MS, Ochsenbauer C, Soderberg K, Liao HX, Montefiori D, Moore P, Johnson S, Koenig S, Haynes BF, Nordstrom JL, Margolis DM, Ferrari G (2015) Dual-affinity re-targeting proteins direct T cell-mediated cytolysis of latently HIV-1-infected cells. J Clin Investig 125(11):4077–4090PubMedGoogle Scholar
  122. Tomaras GD, Yates NL, Liu P, Qin L, Fouda GG, Chavez LL, Decamp AC, Parks RJ, Ashley VC, Lucas JT, Cohen M, Eron J, Hicks CB, Liao HX, Self SG, Landucci G, Forthal DN, Weinhold KJ, Keele BF, Hahn BH, Greenberg ML, Morris L, Karim SS, Blattner WA, Montefiori DC, Shaw GM, Perelson AS, Haynes BF (2008) Initial B-cell responses to transmitted human immunodeficiency virus type 1: virion-binding immunoglobulin M (IgM) and IgG antibodies followed by plasma anti-gp41 antibodies with ineffective control of initial viremia. J Virol 82(24):12449–12463PubMedPubMedCentralGoogle Scholar
  123. Tomescu C, Chehimi J, Maino VC, Montaner LJ (2007) NK cell lysis of HIV-1-infected autologous CD4 primary T cells: requirement for IFN-mediated NK activation by plasmacytoid dendritic cells. Journal of immunology (Baltimore, Md.: 1950) 179(4):2097–2104PubMedGoogle Scholar
  124. van Manen D, Kootstra NA, Boeser-Nunnink B, Handulle MA, van’t Wout AB, Schuitemaker H (2009) Association of HLA-C and HCP5 gene regions with the clinical course of HIV-1 infection. AIDS (London, England) 23(1):19–28PubMedGoogle Scholar
  125. Walker-Sperling VE, Cohen VJ, Tarwater PM, Blankson JN (2015) Reactivation kinetics of HIV-1 and susceptibility of reactivated latently infected CD4+ T Cells to HIV-1-specific CD8+ T Cells. J Virol 89(18):9631–9638PubMedPubMedCentralGoogle Scholar
  126. Walker-Sperling VE, Pohlmeyer CW, Tarwater PM, Blankson JN (2016) The effect of latency reversal agents on primary CD8+ T cells: implications for shock and kill strategies for human immunodeficiency virus eradication. EBioMedicine 8:217–229PubMedPubMedCentralGoogle Scholar
  127. Walker-Sperling VE, Pohlmeyer CW, Veenhuis RT, May M, Luna KA, Kirkpatrick AR, Laeyendecker O, Cox AL, Carrington M, Bailey JR, Arduino RC, Blankson JN (2017) Factors associated with the control of viral replication and virologic breakthrough in a recently infected hiv-1 controller. EBioMedicine 16:141–149PubMedPubMedCentralGoogle Scholar
  128. Wren LH, Chung AW, Isitman G, Kelleher AD, Parsons MS, Amin J, Cooper DA, ADCC study collaboration investigators, Stratov I, Navis M, Kent SJ (2013) Specific antibody-dependent cellular cytotoxicity responses associated with slow progression of HIV-1 infection. Immunology 138(2):116–123PubMedPubMedCentralGoogle Scholar
  129. Yu Q, Konig R, Pillai S, Chiles K, Kearney M, Palmer S, Richman D, Coffin JM, Landau NR (2004) Single-strand specificity of APOBEC3G accounts for minus-strand deamination of the HIV-1 genome. Nat Struct Mol Biol 11(5):435–442Google Scholar
  130. Zhang H, Yang B, Pomerantz RJ, Zhang C, Arunachalam SC, Gao L (2003) The cytidine deaminase CEM15 induces hypermutation in newly synthesized HIV-1 DNA. Nature 424(6944):94–98PubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Center for AIDS Research, Department of MedicineJohns Hopkins University School of MedicineBaltimoreUSA

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