The breadth of expandable memory CD8+ T Cells inversely correlates with residual viral loads in HIV elite controllers

Journal of Virology

Volumn 89, Issue 21, 2015, Pages 10735-10747

  Ndhlovu, Zaza M ^a,d   Stampouloglou, Eleni ^a   Cesa, Kevin ^a   Mavrothalassitis, Orestes ^a   Alvino, Donna Marie ^a   Li, Jonathan Z ^c   Wilton, Shannon ^a   Karel, Daniel ^a   Piechocka Trocha, Alicja ^a   Chen, Huabiao ^e   Pereyra, Florencia ^c   Walker, Bruce D ^a,b,d  

^a HARVARD UNIVERSITY   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

^c BRIGHAM AND WOMEN S HOSPITAL   (United States)

^d UNIVERSITY OF KWAZULU NATAL   (South Africa)

^e MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GAG PROTEIN; HLA ANTIGEN CLASS 1; NEF PROTEIN; VIRUS ENVELOPE PROTEIN;

ARTICLE; CD8+ T LYMPHOCYTE; CLINICAL ARTICLE; CONTROLLED STUDY; CORRELATION ANALYSIS; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IN VIVO STUDY; MEMORY T LYMPHOCYTE; NONHUMAN; POLYMERASE CHAIN REACTION; PRIORITY JOURNAL; VIRUS LOAD; ENZYME LINKED IMMUNOSPOT ASSAY; FLOW CYTOMETRY; IMMUNOLOGICAL MEMORY; IMMUNOLOGY; MASSACHUSETTS; METABOLISM; NONPARAMETRIC TEST; PROCEDURES; REAL TIME POLYMERASE CHAIN REACTION;

CD8-POSITIVE T-LYMPHOCYTES; ENZYME-LINKED IMMUNOSPOT ASSAY; FLOW CYTOMETRY; GENE PRODUCTS, GAG; HIV INFECTIONS; HUMANS; IMMUNOLOGIC MEMORY; MASSACHUSETTS; POLYMERASE CHAIN REACTION; REAL-TIME POLYMERASE CHAIN REACTION; STATISTICS, NONPARAMETRIC; VIRAL LOAD;

EID: 84945205380     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01527-15     Document Type: Article

References (78)

1. Rowland-Jones SL. 2003. Timeline: AIDS pathogenesis. What have two decades of HIV research taught us? Nat Rev Immunol 3:343-348. http://dx.doi.org/10.1038/nri1058.
2. Hazenberg MD, Otto SA, van Benthem BH, Roos MT, Coutinho RA, Lange JM, Hamann D, Prins M, Miedema F. 2003. Persistent immune activation in HIV-1 infection is associated with progression to AIDS. AIDS 17:1881-1888. http://dx.doi.org/10.1097/00002030-200309050-00006.
3. Spijkerman IJ, Prins M, Goudsmit J, Veugelers PJ, Coutinho RA, Miedema F, de Wolf F. 1997. Early and late HIV-1 RNA level and its association with other markers and disease progression in long-term AIDS-free homosexual men. AIDS 11:1383-1388. http://dx.doi.org/10.1097/00002030-199711000-00013.
4. Lyles RH, Munoz A, Yamashita TE, Bazmi H, Detels R, Rinaldo CR, Margolick JB, Phair JP, Mellors JW. 2000. Natural history of human immunodeficiency virus type 1 viremia after seroconversion and proximal to AIDS in a large cohort of homosexual men. Multicenter AIDS Cohort Study. J Infect Dis 181:872-880.
5. Cao Y, Qin L, Zhang L, Safrit J, Ho DD. 1995. Virologic and immunologic characterization of long-term survivors of human immunodefi-ciency virus type 1 infection.NEngl J Med 332:201-208. http://dx.doi.org/10.1056/NEJM199501263320401.
6. Cao Y, Qin L, Zhang L, Safrit J, Ho DD. 1996. Characterization of longterm survivors of human immunodeficiency virus type 1 infection. Immunol Lett 51:7-13. http://dx.doi.org/10.1016/0165-2478(96)02548-5.
7. Deeks SG, Walker BD. 2007. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 27:406-416. http://dx.doi.org/10.1016/j.immuni.2007.08.010.
8. Walker BD, Yu XG. 2013. Unravelling the mechanisms of durable control of HIV-1. Nat Rev Immunol 13:487-498. http://dx.doi.org/10.1038/nri3478.
9. Mothe B, Llano A, Ibarrondo J, Zamarreno J, Schiaulini M, Miranda C, Ruiz-Riol M, Berger CT, Herrero MJ, Palou E, Plana M, Rolland M, Khatri A, Heckerman D, Pereyra F, Walker BD, Weiner D, Paredes R, Clotet B, Felber BK, Pavlakis GN, Mullins JI, Brander C. 2012. CTL responses of high functional avidity and broad variant cross-reactivity are associated with HIV control. PLoS One 7:e29717. http://dx.doi.org/10.1371/journal.pone.0029717.
10. Ndhlovu ZM, Chibnik LB, Proudfoot J, Vine S, McMullen A, Cesa K, Porichis F, Jones RB, Alvino DM, Hart MG, Stampouloglou E, Piechocka-Trocha A, Kadie C, Pereyra F, Heckerman D, De Jager PL, Walker BD, Kaufmann DE. 2013. High-dimensional immunomonitoring models of HIV-1-specific CD8 T-cell responses accurately identify subjects achieving spontaneous viral control. Blood 121:801-811. http://dx.doi.org/10.1182/blood-2012-06-436295.
11. 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-infected long term nonprogressors. Proc Natl Acad Sci U S A 97:2709-2714. http://dx.doi.org/10.1073/pnas.050567397.
12. + T cell proliferation is coupled to perforin expression and is maintained in nonprogressors. Nat Immunol 3:1061-1068. http://dx.doi.org/10.1038/ni845.
13. International HIV 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 DM, Vine S, Addo MM, et al. 2010. The major genetic determinants of HIV-1 control affect HLA class I peptide presentation. Science 330:1551-1557. http://dx.doi.org/10.1126/science.1195271.
14. Autran B, Descours B, Avettand-Fenoel V, Rouzioux C. 2011. Elite controllers as a model of functional cure. Curr Opin HIV AIDS 6:181-187.http://dx.doi.org/10.1097/COH.0b013e328345a328.
15. Julg B, Williams KL, Reddy S, Bishop K, Qi Y, Carrington M, Goulder PJ, Ndung'u T, Walker BD. 2010. Enhanced anti-HIV functional activity associated with Gag-specific CD8 T-cell responses. J Virol 84:5540-5549. http://dx.doi.org/10.1128/JVI.02031-09.
16. Chen H, Piechocka-Trocha A, Miura T, Brockman MA, Julg BD, Baker BM, Rothchild AC, Block BL, Schneidewind A, Koibuchi T, Pereyra F, Allen TM, Walker BD. 2009. Differential neutralization of human immunodeficiency virus (HIV) replication in autologous CD4 T cells by HIV-specific cytotoxic T lymphocytes. J Virol 83:3138-3149. http://dx.doi.org/10.1128/JVI.02073-08.
17. + T-cell responses to different HIV proteins have discordant associations with viral load. Nat Med 13:46-53. http://dx.doi.org/10.1038/nm1520.
18. Staprans SI, Barry AP, Silvestri G, Safrit JT, Kozyr N, Sumpter B, Nguyen H, McClure H, Montefiori D, Cohen JI, Feinberg MB. 2004. Enhanced SIV replication and accelerated progression to AIDS in macaques primed to mount a CD4 T cell response to the SIV envelope protein. Proc Natl Acad Sci U S A 101:13026-13031. http://dx.doi.org/10.1073/pnas.0404739101.
19. Ngumbela KC, Day CL, Mncube Z, Nair K, Ramduth D, Thobakgale C, Moodley E, Reddy S, de Pierres C, Mkhwanazi N, Bishop K, van der Stok M, Ismail N, Honeyborne I, Crawford H, Kavanagh DG, Rousseau C, Nickle D, Mullins J, Heckerman D, Korber B, Coovadia H, Kiepiela P, Goulder PJ, Walker BD. 2008. Targeting of a CD8 T cell env epitope presented by HLA-B*5802 is associated with markers of HIV disease progression and lack of selection pressure. AIDS Res Hum Retroviruses 24: 72-82. http://dx.doi.org/10.1089/aid.2007.0124.
20. Peut V, Kent SJ. 2009. Substantial envelope-specific CD8 T-cell immunity fails to control SIV disease. Virology 384:21-27. http://dx.doi.org/10.1016/j.virol.2008.11.030.
21. Miura T, Brockman MA, Brumme ZL, Brumme CJ, Pereyra F, Trocha A, Block BL, Schneidewind A, Allen TM, Heckerman D, Walker BD. 2009. HLA-associated alterations in replication capacity of chimeric NL4-3 viruses carrying gag-protease from elite controllers of human immunodeficiency virus type 1. J Virol 83:140-149. http://dx.doi.org/10.1128/JVI.01471-08.
22. Miura T, Brumme CJ, Brockman MA, Brumme ZL, Pereyra F, Block BL, Trocha A, John M, Mallal S, Harrigan PR, Walker BD. 2009. HLA-associated viral mutations are common in human immunodeficiency virus type 1 elite controllers. J Virol 83:3407-3412. http://dx.doi.org/10.1128/JVI.02459-08.
23. Miura T, Brumme ZL, Brockman MA, Rosato P, Sela J, Brumme CJ, Pereyra F, Kaufmann DE, Trocha A, Block BL, Daar ES, Connick E, Jessen H, Kelleher AD, Rosenberg E, Markowitz M, Schafer K, Vaida F, Iwamoto A, Little S, Walker BD. 2010. Impaired replication capacity of acute/early viruses in persons who become HIV controllers. J Virol 84: 7581-7591. http://dx.doi.org/10.1128/JVI.00286-10.
24. Wright JK, Naidoo VL, Brumme ZL, Prince JL, Claiborne DT, Goulder PJ, Brockman MA, Hunter E, Ndung'u T. 2012. Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity. J Virol 86:3193-3199. http://dx.doi.org/10.1128/JVI.06682-11.
25. Wright JK, Novitsky V, Brockman MA, Brumme ZL, Brumme CJ, Carlson JM, Heckerman D, Wang B, Losina E, Leshwedi M, van der Stok M, Maphumulo L, Mkhwanazi N, Chonco F, Goulder PJ, Essex M, Walker BD, Ndung'u T. 2011. Influence of Gag-protease-mediated replication capacity on disease progression in individuals recently infected with HIV-1 subtype C. J Virol 85:3996-4006. http://dx.doi.org/10.1128/JVI.02520-10.
26. Martinez-Picado J, Prado JG, Fry EE, Pfafferott K, Leslie A, Chetty S, Thobakgale C, Honeyborne I, Crawford H, Matthews P, Pillay T, Rousseau C, Mullins JI, Brander C, Walker BD, Stuart DI, Kiepiela P, Goulder P. 2006. Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J Virol 80: 3617-3623. http://dx.doi.org/10.1128/JVI.80.7.3617-3623.2006.
27. + T cell escape mutations in simian immunodeficiency virus SIVmac239 cause fitness defects in vivo, and many revert after transmission. J Virol 85:12804-12810. http://dx.doi.org/10.1128/JVI.05841-11.
28. + T cell responses maintain highly functional, broadly directed central memory responses. J Virol 86:6959-6969. http://dx.doi.org/10.1128/JVI.00531-12.
29. 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 infection in the absence of therapy. J Infect Dis 197:563-571. http://dx.doi.org/10.1086/526786.
30. Wilson CC, Wong JT, Girard DD, Merrill DP, Dynan M, An DD, Kalams SA, Johnson RP, Hirsch MS, D'Aquila RT, Walker BD. 1995. Ex vivo expansion of CD4 lymphocytes from human immunodeficiency virus type 1-infected persons in the presence of combination antiretroviral agents. J Infect Dis 172:88-96. http://dx.doi.org/10.1093/infdis/172.1.88.
31. Palmer S, Wiegand AP, Maldarelli F, Bazmi H, Mican JM, Polis M, Dewar RL, Planta A, Liu S, Metcalf JA, Mellors JW, Coffin JM. 2003. New real-time reverse transcriptase-initiated PCR assay with single-copy sensitivity for human immunodeficiency virus type 1 RNA in plasma. JClin Microbiol 41:4531-4536. http://dx.doi.org/10.1128/JCM.41.10.4531-4536.2003.
32. Geldmacher C, Currier JR, Herrmann E, Haule A, Kuta E, McCutchan F, Njovu L, Geis S, Hoffmann O, Maboko L, Williamson C, Birx D, Meyerhans A, Cox J, Hoelscher M. 2007. CD8 T-cell recognition of multiple epitopes within specific Gag regions is associated with maintenance of a low steady-state viremia in human immunodeficiency virus type 1-seropositive patients. J Virol 81:2440-2448. http://dx.doi.org/10.1128/JVI.01847-06.
33. + T-cell responses to the gag protein of human immunodeficiency virus type 1 correlates inversely with viral load in plasma. J Virol 76:2298-2305. http://dx.doi.org/10.1128/jvi.76.5.2298-2305.2002.
34. Ranasinghe S, Cutler S, Davis I, Lu R, Soghoian DZ, Qi Y, Sidney J, Kranias G, Flanders MD, Lindqvist M, Kuhl B, Alter G, Deeks SG, Walker BD, Gao X, Sette A, Carrington M, Streeck H. 2013. Association of HLA-DRB1-restricted CD4(+) T cell responses with HIV immune control. Nat Med 19:930-933. http://dx.doi.org/10.1038/nm.3229.
35. Jia M, Hong K, Chen J, Ruan Y, Wang Z, Su B, Ren G, Zhang X, Liu Z, Zhao Q, Li D, Peng H, Altfeld M, Walker BD, Yu XG, Shao Y. 2012. Preferential CTL targeting of Gag is associated with relative viral control in long-term surviving HIV-1 infected former plasma donors from China. Cell Res 22:903-914. http://dx.doi.org/10.1038/cr.2012.19.
36. + T-cell epitopes in acute clade C virus infection. J Infect Dis 204:768-776. http://dx.doi.org/10.1093/infdis/jir394.
37. Mlotshwa M, Riou C, Chopera D, de Assis Rosa D, Ntale R, Treunicht F, Woodman Z, Werner L, van Loggerenberg F, Mlisana K, Abdool Karim S, Williamson C, Gray CM, CAPRISA 002 Study Team. 2010. Fluidity of HIV-1-specific T-cell responses during acute and early subtype C HIV-1 infection and associations with early disease progression. J Virol 84:12018-12029. http://dx.doi.org/10.1128/JVI.01472-10.
38. Lichterfeld M, Yu XG, Cohen D, Addo MM, Malenfant J, Perkins B, Pae E, Johnston MN, Strick D, Allen TM, Rosenberg ES, Korber B, Walker BD, Altfeld M. 2004. HIV-1 Nef is preferentially recognized by CD8 T cells in primary HIV-1 infection despite a relatively high degree of genetic diversity. AIDS 18:1383-1392. http://dx.doi.org/10.1097/01.aids.0000131329.51633.a3.
39. Kim GJ, Lee HS, Hong KJ, Kim SS. 2010. Dynamic correlation between CTL response and viral load in primary human immunodeficiency virus-1 infected Koreans. Virol J 7:239. http://dx.doi.org/10.1186/1743-422X-7-239.
40. Letvin NL, Montefiori DC, Yasutomi Y, Perry HC, Davies ME, Lekutis C, Alroy M, Freed DC, Lord CI, Handt LK, Liu MA, Shiver JW. 1997. Potent, protective anti-HIV immune responses generated by bimodal HIV envelope DNA plus protein vaccination. Proc Natl Acad Sci U S A 94:9378-9383. http://dx.doi.org/10.1073/pnas.94.17.9378.
41. Bell SJ, Cooper DA, Kemp BE, Doherty RR, Penny R. 1992. Definition of an immunodominant T cell epitope contained in the envelope gp41 sequence of HIV-1. Clin Exp Immunol 87:37-45.
42. Belyakov IM, Ahlers JD, Brandwein BY, Earl P, Kelsall BL, Moss B, Strober W, Berzofsky JA. 1998. The importance of local mucosal HIVspecific CD8(+) cytotoxic T lymphocytes for resistance to mucosal viral transmission in mice and enhancement of resistance by local administration of IL-12. J Clin Invest 102:2072-2081. http://dx.doi.org/10.1172/JCI5102.
43. Zhuang Y, Sun Y, Zhai S, Huang D, Zhao S, Wang S, Kang W, Li X, Walker BD, Altfeld M, Yu XG. 2008. Relative dominance of Envgp41-specific cytotoxic T lymphocytes responses in HIV-1 advanced infection. Curr HIV Res 6:239-245. http://dx.doi.org/10.2174/157016208784324921.
44. + T cells is required for HIV-infected cell elimination associated with immune control. Immunity 29:1009-1021. http://dx.doi.org/10.1016/j.immuni.2008.10.010.
45. + T-cell polyfunctionality, proliferation, and cytotoxicity are not restored by antiretroviral therapy. J Virol 83: 11876-11889. http://dx.doi.org/10.1128/JVI.01153-09.
46. + T-cell response associated with immunologic control. Curr Opin HIV AIDS 6:169-173. http://dx.doi.org/10.1097/COH.0b013e3283454c39.
47. Chen H, Ndhlovu ZM, Liu D, Porter LC, Fang JW, Darko S, Brockman MA, Miura T, Brumme ZL, Schneidewind A, Piechocka-Trocha A, Cesa KT, Sela J, Cung TD, Toth I, Pereyra F, Yu XG, Douek DC, Kaufmann DE, Allen TM, Walker BD. 2012. TCR clonotypes modulate the protective effect of HLA class I molecules in HIV-1 infection. Nat Immunol 13:691-700. http://dx.doi.org/10.1038/ni.2342.
48. Pereyra F, Palmer S, Miura T, Block BL, Wiegand A, Rothchild AC, Baker B, Rosenberg R, Cutrell E, Seaman MS, Coffin JM, Walker BD. 2009. Persistent low-level viremia in HIV-1 elite controllers and relationship to immunologic parameters. J Infect Dis 200:984-990. http://dx.doi.org/10.1086/605446.
49. Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, Kingsley LA, Todd JA, Saah AJ, Detels R, Phair JP, Rinaldo CR, Jr. 1997. Plasma viral load and CD4+ lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 126:946-954. http://dx.doi.org/10.7326/0003-4819-126-12-199706150-00003.
50. Arnaout RA, Lloyd AL, O'Brien TR, Goedert JJ, Leonard JM, Nowak MA. 1999. A simple relationship between viral load and survival time in HIV-1 infection. Proc Natl Acad Sci U S A 96:11549-11553. http://dx.doi.org/10.1073/pnas.96.20.11549.
51. Barouch DH, Kunstman J, Kuroda MJ, Schmitz JE, Santra S, Peyerl FW, Krivulka GR, Beaudry K, Lifton MA, Gorgone DA, Montefiori DC, Lewis MG, Wolinsky SM, Letvin NL. 2002. Eventual AIDS vaccine failure in a rhesus monkey by viral escape from cytotoxic T lymphocytes. Nature 415:335-339. http://dx.doi.org/10.1038/415335a.
52. Phillips RE, Rowland-Jones S, Nixon DF, Gotch FM, Edwards JP, Ogunlesi AO, Elvin JG, Rothbard JA, Bangham CR, Rizza CR, Mc-Michael AJ. 1991. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature 354:453-459. http://dx.doi.org/10.1038/354453a0.
53. Koenig S, Conley AJ, Brewah YA, Jones GM, Leath S, Boots LJ, Davey V, Pantaleo G, Demarest JF, Carter C, Wannebo C, Yannelli JR, Rosenberg SA, Lane HC. 1995. Transfer of HIV-1-specific cytotoxic T lymphocytes to an AIDS patient leads to selection for mutant HIV variants and subsequent disease progression. Nat Med 1:330-336. http://dx.doi.org/10.1038/nm0495-330.
54. Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G, Nowak MA, Giangrande P, Luzzi G, Morgan B, Edwards A, McMichael AJ, Rowland-Jones S. 1997. Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 3:212-217. http://dx.doi.org/10.1038/nm0297-212.
55. Goulder PJ, Brander C, Tang Y, Tremblay C, Colbert RA, Addo MM, Rosenberg ES, Nguyen T, Allen R, Trocha A, Altfeld M, He S, Bunce M, Funkhouser R, Pelton SI, Burchett SK, McIntosh K, Korber BT, Walker BD. 2001. Evolution and transmission of stable CTL escape mutations in HIV infection. Nature 412:334-338. http://dx.doi.org/10.1038/35085576.
56. + T-cell responses following cytotoxic T-lymphocyte escape in chronic human immunodeficiency virus type 1 infection. J Virol 79:12952-12960. http://dx.doi.org/10.1128/JVI.79.20.12952-12960.2005.
57. Miura T, Brockman MA, Schneidewind A, Lobritz M, Pereyra F, Rathod A, Block BL, Brumme ZL, Brumme CJ, Baker B, Rothchild AC, Li B, Trocha A, Cutrell E, Frahm N, Brander C, Toth I, Arts EJ, Allen TM, Walker BD. 2009. HLA-B57/B*5801 human immunodeficiency virus type 1 elite controllers select for rare Gag variants associated with reduced viral replication capacity and strong cytotoxic T-lymphotye [sic] recognition. J Virol 83:2743-2755. http://dx.doi.org/10.1128/JVI.02265-08.
58. Brumme ZL, Brumme CJ, Carlson J, Streeck H, John M, Eichbaum Q, Block BL, Baker B, Kadie C, Markowitz M, Jessen H, Kelleher AD, Rosenberg E, Kaldor J, Yuki Y, Carrington M, Allen TM, Mallal S, Altfeld M, Heckerman D, Walker BD. 2008. Marked epitope-and allele-specific differences in rates of mutation in human immunodeficiency type 1 (HIV-1) Gag, Pol, and Nef cytotoxic T-lymphocyte epitopes in acute/ early HIV-1 infection. J Virol 82:9216-9227. http://dx.doi.org/10.1128/JVI.01041-08.
59. Feeney ME, Tang Y, Pfafferott K, Roosevelt KA, Draenert R, Trocha A, Yu XG, Verrill C, Allen T, Moore C, Mallal S, Burchett S, McIntosh K, Pelton SI, St John MA, Hazra R, Klenerman P, Altfeld M, Walker BD, Goulder PJ. 2005. HIV-1 viral escape in infancy followed by emergence of a variant-specific CTL response. J Immunol 174:7524-7530. http://dx.doi.org/10.4049/jimmunol.174.12.7524.
60. Streeck H, Schweighardt B, Jessen H, Allgaier RL, Wrin T, Stawiski EW, Jessen AB, Allen TM, Walker BD, Altfeld M. 2007. Loss of HIV-1-specific T-cell responses associated with very rapid HIV-1 disease progression. AIDS 21:889-891. http://dx.doi.org/10.1097/QAD.0b013e3280f77439.
61. Boutwell CL, Carlson JM, Lin TH, Seese A, Power KA, Peng J, Tang Y, Brumme ZL, Heckerman D, Schneidewind A, Allen TM. 2013. Frequent and variable cytotoxic-T-lymphocyte escape-associated fitness costs in the human immunodeficiency virus type 1 subtype B Gag proteins. J Virol 87:3952-3965. http://dx.doi.org/10.1128/JVI.03233-12.
62. Borrow P, Lewicki H, Wei X, Horwitz MS, Peffer N, Meyers H, Nelson JA, Gairin JE, Hahn BH, Oldstone MB, Shaw GM. 1997. Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 3:205-211. http://dx.doi.org/10.1038/nm0297-205.
63. Leslie AJ, Pfafferott KJ, Chetty P, Draenert R, Addo MM, Feeney M, Tang Y, Holmes EC, Allen T, Prado JG, Altfeld M, Brander C, Dixon C, Ramduth D, Jeena P, Thomas SA, St John A, Roach TA, Kupfer B, Luzzi G, Edwards A, Taylor G, Lyall H, Tudor-Williams G, Novelli V, Martinez-Picado J, Kiepiela P, Walker BD, Goulder PJ. 2004. HIV evolution: CTL escape mutation and reversion after transmission. Nat Med 10:282-289. http://dx.doi.org/10.1038/nm992.
64. + T-cell recognition of simian immunodeficiency virus-infected cells expressing the same variant sequences. J Virol 82:575-581. http://dx.doi.org/10.1128/JVI.00275-07.
65. + T cells from HLA-B*57 elite suppressors effectively suppress replication of HIV-1 escape mutants. Retrovirology 10:152. http://dx.doi.org/10.1186/1742-4690-10-152.
66. Dahirel V, Shekhar K, Pereyra F, Miura T, Artyomov M, Talsania S, Allen TM, Altfeld M, Carrington M, Irvine DJ, Walker BD, Chakraborty AK. 2011. Coordinate linkage of HIV evolution reveals regions of immunological vulnerability. Proc Natl Acad Sci U S A 108: 11530-11535. http://dx.doi.org/10.1073/pnas.1105315108.
67. Tang Y, Huang S, Dunkley-Thompson J, Steel-Duncan JC, Ryland EG, St John MA, Hazra R, Christie CD, Feeney ME. 2010. Correlates of spontaneous viral control among long-term survivors of perinatal HIV-1 infection expressing human leukocyte antigen-B57. AIDS 24:1425-1435. http://dx.doi.org/10.1097/QAD.0b013e32833a2b5b.
68. Balamurugan A, Ali A, Boucau J, Le Gall S, Ng HL, Yang OO. 2013. HIV-1 Gag cytotoxic T lymphocyte epitopes vary in presentation kinetics relative to HLA class I downregulation. J Virol 87:8726-8734. http://dx.doi.org/10.1128/JVI.01040-13.
69. Ali A, Lubong R, Ng H, Brooks DG, Zack JA, Yang OO. 2004. Impacts of epitope expression kinetics and class I downregulation on the antiviral activity of human immunodeficiency virus type 1-specific cytotoxic T lymphocytes. J Virol 78:561-567. http://dx.doi.org/10.1128/JVI.78.2.561-567.2004.
70. Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, Abraha A, Tebit DM, Zhao H, Avila S, Lobritz MA, McElrath MJ, Le Gall S, Mullins JI, Arts EJ. 2009. Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog 5:e1000365. http://dx.doi.org/10.1371/journal.ppat.1000365.
71. Fu TM, Dubey SA, Mehrotra DV, Freed DC, Trigona WL, Adams-Muhler L, Clair JH, Evans TG, Steigbigel R, Jacobson JM, Goepfert PA, Mulligan MJ, Kalams SA, Rinaldo C, Zhu L, Cox KS, Guan L, Long R, Persaud N, Caulfield MJ, Sadoff JC, Emini EA, Thaler S, Shiver JW. 2007. Evaluation of cellular immune responses in subjects chronically infected with HIV type 1. AIDS Res Hum Retroviruses 23:67-76. http://dx.doi.org/10.1089/aid.2006.0114.
72. Addo MM, Yu XG, Rathod A, Cohen D, Eldridge RL, Strick D, Johnston MN, Corcoran C, Wurcel AG, Fitzpatrick CA, Feeney ME, Rodriguez WR, Basgoz N, Draenert R, Stone DR, Brander C, Goulder PJ, Rosenberg ES, Altfeld M, Walker BD. 2003. Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J Virol 77:2081-2092. http://dx.doi.org/10.1128/JVI.77.3.2081-2092.2003.
73. Freel SA, Lamoreaux L, Chattopadhyay PK, Saunders K, Zarkowsky D, Overman RG, Ochsenbauer C, Edmonds TG, Kappes JC, Cunningham CK, Denny TN, Weinhold KJ, Ferrari G, Haynes BF, Koup RA, Graham BS, Roederer M, Tomaras GD. 2010. Phenotypic and functional profile of HIV-inhibitory CD8 T cells elicited by natural infection and heterologous prime/boost vaccination. J Virol 84:4998-5006. http://dx.doi.org/10.1128/JVI.00138-10.
74. + T cells in HIV-1-infected elite suppressors. J Virol 86:13679-13688. http://dx.doi.org/10.1128/JVI.02439-12.
75. Masopust D, Picker LJ. 2012. Hidden memories: frontline memory T cells and early pathogen interception. J Immunol 188:5811-5817. http://dx.doi.org/10.4049/jimmunol.1102695.
76. 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 473:523-527. http://dx.doi.org/10.1038/nature10003.
77. + T cell epitope recognition paradigms. Science 340:1237874. http://dx.doi.org/10.1126/science.1237874.
78. Hansen SG, Vieville C, Whizin N, Coyne-Johnson L, Siess DC, Drummond DD, Legasse AW, Axthelm MK, Oswald K, Trubey CM, Piatak M, Jr, Lifson JD, Nelson JA, Jarvis MA, Picker LJ. 2009. Effector memory T cell responses are associated with protection of rhesus monkeys from mucosal simian immunodeficiency virus challenge. Nat Med 15: 293-299. http://dx.doi.org/10.1038/nm.1935.