HIV control is mediated in part by CD8+ T-cell targeting of specific epitopes

Journal of Virology

Volumn 88, Issue 22, 2014, Pages 12937-12948

  Pereyra, Florencia ^a,b   Heckerman, David ^c   Carlson, Jonathan M ^c   Kadie, Carl ^c   Soghoian, Damien Z ^a   Karel, Daniel ^a   Goldenthal, Ariel ^a   Davis, Oliver B ^a   DeZiel, Charles E ^c   Lin, Tienho ^c   Peng, Jian ^c   Piechocka, Alicja ^a   Carrington, Mary ^a,d   Walker, Bruce D ^a,e  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b BRIGHAM AND WOMEN S HOSPITAL   (United States)

^c MICROSOFT RESEARCH   (United States)

^d FREDERICK NATIONAL LABORATORY FOR CANCER RESEARCH   (United States)

^e HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; GAMMA INTERFERON; HLA ANTIGEN CLASS 1;

ADULT; ALLELE; AMINO ACID SEQUENCE; ARTICLE; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; ENZYME LINKED IMMUNOSPOT ASSAY; FEMALE; GENE MUTATION; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNE SYSTEM; INFECTION CONTROL; MAJOR CLINICAL STUDY; MALE; MIDDLE AGED; PROTEIN DETERMINATION; PROTEIN STABILITY; PROTEIN STRUCTURE; PROTEIN TARGETING; VIREMIA; YOUNG ADULT; BIOLOGY; COHORT ANALYSIS; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; SECRETION (PROCESS);

ADULT; CD8-POSITIVE T-LYMPHOCYTES; COHORT STUDIES; COMPUTATIONAL BIOLOGY; ENZYME-LINKED IMMUNOSPOT ASSAY; EPITOPES; FEMALE; HISTOCOMPATIBILITY ANTIGENS CLASS I; HIV INFECTIONS; HIV-1; HUMANS; INTERFERON-GAMMA; MALE; MIDDLE AGED;

EID: 84908123252     PISSN: 0022538X     EISSN: 10985514     Source Type: Journal    
DOI: 10.1128/JVI.01004-14     Document Type: Article

References (91)

1. Kaslow RA, Carrington M, Apple R, Park L, Muñoz A, Saah AJ, Goedert JJ, Winkler C, O'Brien SJ, Rinaldo C, Detels R, Blattner W, Phair J, Erlich H, Mann DL. 1996. Influence of combinations of human major histocompatibility complex genes on the course of HIV-1 infection. Nat. Med. 2:405-411. http://dx.doi.org/10.1038/nm0496-405.
2. Carrington M, Nelson GW, Martin MP, Kissner T, Vlahov D, Goedert JJ, Kaslow R, Buchbinder S, Hoots K, O'Brien SJ. 1999. HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283: 1748-1752. http://dx.doi.org/10.1126/science.283.5408.1748.
3. 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 SA, 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 wholegenome association study of major determinants for host control of HIV-1. Science 317:944-947. http://dx.doi.org/10.1126/science.1143767.
4. Goulder PJR, Walker BD. 2012. HIV and HLA class I: an evolving relationship. Immunity 37:426-440. http://dx.doi.org/10.1016/j.immuni.2012.09.005.
5. Pereyra F, Jia X, McLaren PJ, Telenti A, de Bakker PIW, 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 DML, Vine S, Addo MM, Allen TM, 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.
6. 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 283:857-860. http://dx.doi.org/10.1126/science.283.5403.857.
7. + 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.
8. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, Mackey EW, Miller JD, Leslie AJ, DePierres C, Mncube Z, Duraiswamy J, Zhu B, Eichbaum Q, Altfeld M, Wherry EJ, Coovadia HM, Goulder PJR, Klenerman P, Ahmed R, Freeman GJ, Walker BD. 2006. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443:350-354. http://dx.doi.org/10.1038/nature05115.
9. Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, Boulassel M-R, Delwart E, Sepulveda H, Balderas RS, Routy J-P, Haddad EK, Sekaly R-P. 2006. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat. Med. 12:1198-1202. http://dx.doi.org/10.1038/nm1482.
10. Sáez-Cirión A, Lacabaratz C, Lambotte O, Versmisse P, Urrutia A, Boufassa F, Barré-Sinoussi F, Delfraissy J-F, Sinet M, Pancino G, Venet A. 2007. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc. Natl. Acad. Sci. U. S. A. 104:6776-6781. http://dx.doi.org/10.1073/pnas.0611244104.
11. 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.
12. Buchbinder SP, Mehrotra DV, Duerr A, Fitzgerald DW, Mogg R, Li D, Gilbert PB, Lama JR, Marmor M, Del Rio C, McElrath MJ, Casimiro DR, Gottesdiener KM, Chodakewitz JA, Corey L, Robertson MN. 2008. Efficacy assessment of a cell-mediated immunity HIV-1 vaccine (the Step Study): a double-blind, randomised, placebo-controlled, test-of-concept trial. Lancet 372:1881-1893. http://dx.doi.org/10.1016/S0140-6736(08) 61591-3.
13. Hammer SM, Sobieszczyk ME, Janes H, Karuna ST, Mulligan MJ, Grove D, Koblin BA, Buchbinder SP, Keefer MC, Tomaras GD, Frahm N, Hural J, Anude C, Graham BS, Enama ME, Adams E, DeJesus E, Novak RM, Frank I, Bentley C, Ramirez S, Fu R, Koup RA, Mascola JR, Nabel GJ, Montefiori DC, Kublin J, McElrath MJ, Corey L, Gilbert PB. 2013. Efficacy trial of a DNA/rAd5 HIV-1 preventive vaccine. N. Engl. J. Med. 369:2083-2092. http://dx.doi.org/10.1056/NEJMoa1310566.
14. Kiepiela P, Ngumbela K, Thobakgale C, Ramduth D, Honeyborne I, Moodley E, Reddy S, de Pierres C, Mncube Z, Mkhwanazi N, Bishop K, van der Stok M, Nair K, Khan N, Crawford H, Payne R, Leslie AJ, Prado J, Prendergast A, Frater J, McCarthy N, Brander C, Learn GH, Nickle D, Rousseau C, Coovadia H, Mullins JI, Heckerman D, Walker BD, Goulder PJR. 2007. CD8+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.
15. Rolland M, Heckerman D, Deng W, Rousseau CM, Coovadia H, Bishop K, Goulder PJR, Walker BD, Brander C, Mullins JI. 2008. Broad and Gagbiased HIV-1 epitope repertoires are associated with lower viral loads. PLoS One 3:e1424. http://dx.doi.org/10.1371/journal.pone.0001424.
16. Huang K-HG, Goedhals D, Carlson JM, Brockman MA, Mishra S, Brumme ZL, Hickling S, Tang CSW, Miura T, Seebregts C, Heckerman D, Ndung'u T, Walker BD, Klenerman P, Steyn D, Goulder PJR, Phillips R, van Vuuren C, Frater J. 2011. Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations. PLoS One 6:e19018. http://dx.doi.org/10.1371/journal.pone.0019018.
17. Zuñiga R, Lucchetti A, Galvan P, Sanchez C, Hernandez A, Sanchez H, Frahm N, Linde CH, Hewitt HS, Altfeld M, Allen TM, Walker BD, Korber BT, Leitner T, Sanchez J, Brander C, Sanchez S, Hildebrand W. 2006. Relative dominance of Gag p24-specific cytotoxic T lymphocytes is associated with human immunodeficiency virus control. J. Virol. 80: 3122-3125. http://dx.doi.org/10.1128/JVI.80.6.3122-3125.2006.
18. + T lymphocytes recognize infected cells before AIDSvirus integration and viral protein expression. J. Immunol. 178:2746-2754. http://dx.doi.org/10.4049/jimmunol.178.5.2746.
19. Heckerman DE, Frahm N, Pereyra F, Dubey S, Geraghty DE, Carlson JM, Robertson MN, McElrath MJ, Casimiro DR, Walker BD. 2009. Vaccine-induced targeting of epitopes associated with spontaneous control of HIV viral replication is assocaited with lower set-point viral loads in HIV-infected participants from the STEP trial, p 95. In 16th Conf. Retroviruses Opportun. Infect., Montreal, Canada.
20. Rolland M, Nickle DC, Mullins JI. 2007. HIV-1 group M conserved elements vaccine. PLoS Pathog. 3:e157. http://dx.doi.org/10.1371/journal.ppat.0030157.
21. + T-cell responses better define HIV disease progression than HLA genotype. J. Virol. 84: 4461-4468. http://dx.doi.org/10.1128/JVI.02438-09.
22. 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.
23. Mothe B, Llano A, Ibarrondo J, Zamarreño 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.
24. Ferguson AL, Mann JK, Omarjee S, Ndung'u T, Walker BD, Chakraborty AK. 2013. Translating HIV sequences into quantitative fitness landscapes predicts viral vulnerabilities for rational immunogen design. Immunity 38:606-617. http://dx.doi.org/10.1016/j.immuni.2012.11.022.
25. Mothe B, Llano A, Ibarrondo J, Daniels M, Miranda C, Zamarreño J, Bach V, Zuniga R, Pérez-álvarez S, Berger CT, Puertas MC, Martinez-Picado J, Rolland M, Farfan M, Szinger JJ, Hildebrand WH, Yang OO, Sanchez-Merino V, Brumme CJ, Brumme ZL, Heckerman D, Allen TM, Mullins JI, Gómez G, Goulder PJ, Walker BD, Gatell JM, Clotet B, Korber BT, Sanchez J, Brander C. 2011. Definition of the viral targets of protective HIV-1-specific T cell responses. J. Transl. Med. 9:208. http://dx.doi.org/10.1186/1479-5876-9-208.
26. Navis M, Schellens IMM, van Swieten P, Borghans JAM, Miedema F, Kootstra NA, van Baarle D, Schuitemaker H. 2008. A nonprogressive clinical course in HIV-infected individuals expressing human leukocyte antigen B57/5801 is associated with preserved CD8+ T lymphocyte responsiveness to the HW9 epitope in Nef. J. Infect. Dis. 197:871-879. http://dx.doi.org/10.1086/528695.
27. Adland E, Carlson JM, Paioni P, Kløverpris H, Shapiro R, Ogwu A, Riddell L, Luzzi G, Chen F, Balachandran T, Heckerman D, Stryhn A, Edwards A, Ndung'u T, Walker BD, Buus S, Goulder P, Matthews PC. 2013. Nef-specific CD8+ T cell responses contribute to HIV-1 immune control. PLoS One 8:e73117. http://dx.doi.org/10.1371/journal.pone.0073117.
28. Létourneau S, Im E-J, Mashishi T, Brereton C, Bridgeman A, Yang H, Dorrell L, Dong T, Korber B, McMichael AJ, Hanke T. 2007. Design and pre-clinical evaluation of a universal HIV-1 vaccine. PLoS One 2:e984. http://dx.doi.org/10.1371/journal.pone.0000984.
29. Hansen JA (ed). 2005. Immunobiology of the human MHC: 13th International Histocompatibility Workshop and Congress. IHWG Press, Seattle, WA.
30. Sidney J, Peters B, Frahm N, Brander C, Sette A. 2008. HLA class I supertypes: a revised and updated classification.BMCImmunol. 9:1. http://dx.doi.org/10.1186/1471-2172-9-1.
31. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, Rathnavalu P, Moore C, Pfafferott KJ, Hilton L, Zimbwa P, Moore S, Allen T, Brander C, Addo MM, Altfeld M, James I, Mallal SA, Bunce M, Barber LD, Szinger J, Day C, Klenerman P, Mullins JI, Korber B, Coovadia HM, Walker BD, Goulder PJR. 2004. Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432:769-775. http://dx.doi.org/10.1038/nature03113.
32. Kloverpris HN, Stryhn A, Harndahl M, van der Stok M, Payne RP, Matthews PC, Chen F, Riddell L, Walker BD, Ndung'u T, Buus S, Goulder PJR. 2012. HLA-B*57 micropolymorphism shapes HLA allelespecific epitope immunogenicity, selection pressure, and HIV immune control. J. Virol. 86:919-929. http://dx.doi.org/10.1128/JVI.06150-11.
33. Gao X, Nelson GW, Karacki P, Martin MP, Phair J, Kaslow R, Goedert JJ, Buchbinder S, Hoots K, Vlahov D, O'Brien SJ, Carrington M. 2001. Effect of a single amino acid change in MHC class I molecules on the rate of progression to AIDS. N. Engl. J. Med. 344:1668-1675. http://dx.doi.org/10.1056/NEJM200105313442203.
34. Kløverpris HN, Harndahl M, Leslie AJ, Carlson JM, Ismail N, van der Stok M, Huang K-HG, Chen F, Riddell L, Steyn D, Goedhals D, van Vuuren C, Frater J, Walker BD, Carrington M, Ndung'u T, Buus S, Goulder PJR. 2012. HIV control through a single nucleotide on the HLA-B locus. J. Virol. 86:11493-11500. http://dx.doi.org/10.1128/JVI.01020-12.
35. Frahm N, Baker B, Brander C. 2008. Identification and optimal definition of HIV-derived cytotoxic T lymphocyte (CTL) epitopes for the study of CTL escape, functional avidity and viral evolution, p 3-24. In Korber BT, Brander C, Haynes BF, Koup RA, Moore JP, Walker BD, Watkins DI (ed), HIV molecular immunology 2008. Los Alamos National Laboratory, Theoretical Biology and Biophysics, Los Alamos, NM.
36. 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 PJR, Rosenberg ES, Altfeld M, Walker BD, Irol JV. 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.
37. Feeney ME, Roosevelt KA, Tang Y, Pfafferott KJ, McIntosh K, Burchett SK, Mao C, Walker BD, Goulder PJR. 2003. Comprehensive screening reveals strong and broadly directed human immunodeficiency virus type 1-specific CD8 responses in perinatally infected children. J. Virol. 77: 7492-7501. http://dx.doi.org/10.1128/JVI.77.13.7492-7501.2003.
38. Soghoian DZ, Jessen H, Flanders M, Sierra-Davidson K, Cutler S, Pertel T, Ranasinghe S, Lindqvist M, Davis I, Lane K, Rychert J, Rosenberg ES, Piechocka-Trocha A, Brass AL, Brenchley JM, Walker BD, Streeck H. 2012. HIV-specific cytolytic CD4 T cell responses during acute HIV infection predict disease outcome. Sci. Transl. Med. 4:123ra25. http://dx.doi.org/10.1126/scitranslmed.3003165.
39. Andrew G, Gao J. 2007. Scalable training of L1-regularized log-linear models, p 33-40. In Proceedings of the 24th International Conference on Machine Learning. ACM Press, New York, NY.
40. Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez J-C, Müller M. 2011. pROC: an open-source package for R and S+ to analyze and compare ROC curves. BMC Bioinformatics 12:77. http://dx.doi.org/10.1186/1471-2105-12-77.
41. Frahm N, Yusim K, Suscovich TJ, Adams S, Sidney J, Hraber P, Hewitt HS, Linde CH, Kavanagh DG, Woodberry T, Henry LM, Faircloth K, Listgarten J, Kadie C, Jojic N, Sango K, Brown NV, Pae E, Zaman MT, Bihl F, Khatri A, John M, Mallal SA, Marincola FM, Walker BD, Sette A, Heckerman D, Korber BT, Brander C. 2007. Extensive HLA class I allele promiscuity among viral CTL epitopes. Eur. J. Immunol. 37:2419-2433. http://dx.doi.org/10.1002/eji.200737365.
42. Carlson JM, Heckerman D. 2009. Estimating false discovery rates for contingency tables. Microsoft Res. MSR-TR-2009-53.
43. Spirtes P, Glymour CN, Scheines R. 2000. Causation, prediction, and search. MIT Press, Cambridge, MA.
44. Boutwell CL, Carlson JM, Lin T-H, 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.
45. Kelly BN, Howard BR, Wang H, Robinson H, Sundquist WI, Hill CP. 2006. Implications for viral capsid assembly from crystal structures of HIV-1 Gag(1-278) and CA(N)(133-278). Biochemistry 45:11257-11266. http://dx.doi.org/10.1021/bi060927x.
46. Pornillos O, Ganser-Pornillos BK, Kelly BN, Hua Y, Whitby FG, Stout CD, Sundquist WI, Hill CP, Yeager M. 2009. X-ray structures of the hexameric building block of the HIV capsid. Cell 137:1282-1292. http://dx.doi.org/10.1016/j.cell.2009.04.063.
47. Robbins AH, Coman RM, Bracho-Sanchez E, Fernandez MA, Gilliland CT, Li M, Agbandje-McKenna M, Wlodawer A, Dunn BM, McKenna R. 2010. Structure of the unbound form of HIV-1 subtype A protease: comparison with unbound forms of proteases from other HIV subtypes. Acta Crystallogr. D Biol. Crystallogr. 66:233-242. http://dx.doi.org/10.1107/S0907444909054298.
48. Hsiou Y, Ding J, Das K, Clark AD, Hughes SH, Arnold E. 1996. Structure of unliganded HIV-1 reverse transcriptase at 2.7 A resolution: implications of conformational changes for polymerization and inhibition mechanisms. Structure 4:853-860. http://dx.doi.org/10.1016/S0969-2126(96)00091-3.
49. Goldgur Y, Dyda F, Hickman AB, Jenkins TM, Craigie R, Davies DR. 1998. Three new structures of the core domain of HIV-1 integrase: an active site that binds magnesium. Proc. Natl. Acad. Sci. U. S. A. 95:9150-9154. http://dx.doi.org/10.1073/pnas.95.16.9150.
50. Tahirov TH, Babayeva ND, Varzavand K, Cooper JJ, Sedore SC, Price DH. 2010. Crystal structure of HIV-1 Tat complexed with human P-TEFb. Nature 465:747-751. http://dx.doi.org/10.1038/nature09131.
51. Daugherty MD, Liu B, Frankel AD. 2010. Structural basis for cooperative RNA binding and export complex assembly by HIV Rev. Nat. Struct. Mol. Biol. 17:1337-1342. http://dx.doi.org/10.1038/nsmb.1902.
52. Lee CH, Saksela K, Mirza UA, Chait BT, Kuriyan J. 1996. Crystal structure of the conserved core of HIV-1 Nef complexed with a Src family SH3 domain. Cell 85:931-942. http://dx.doi.org/10.1016/S0092-8674(00) 81276-3.
53. Pancera M, Majeed S, Ban Y-EA, Chen L, Huang C, Kong L, Kwon Do Y, Stuckey J, Zhou T, Robinson JE, Schief WR, Sodroski J, Wyatt R, Kwong PD. 2010. Structure of HIV-1 gp120 with gp41-interactive region reveals layered envelope architecture and basis of conformational mobility. Proc. Natl. Acad. Sci. U. S. A. 107:1166-1171. http://dx.doi.org/10.1073/pnas.0911004107.
54. Guerois R, Nielsen JE, Serrano L. 2002. Predicting changes in the stability of proteins and protein complexes: a study of more than 1000 mutations. J. Mol. Biol. 320:369-387. http://dx.doi.org/10.1016/S0022-2836(02) 00442-4.
55. Carlson JM, Brumme CJ, Martin E, Listgarten J, Brockman MA, Le AQ, Chui CKS, Cotton LA, Knapp DJHF, Riddler SA, Haubrich R, Nelson G, Pfeifer N, Deziel CE, Heckerman D, Apps R, Carrington M, Mallal S, Harrigan PR, John M, Brumme ZL. 2012. Correlates of protective cellular immunity revealed by analysis of population-level immune escape pathways in HIV-1. J. Virol. 86:13202-13216. http://dx.doi.org/10.1128/JVI.01998-12.
56. 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.
57. Frahm N, Kiepiela P, Adams S, Linde CH, Hewitt HS, Sango K, Feeney ME, Addo MM, Lichterfeld M, Lahaie MP, Pae E, Wurcel AG, Roach T, St John MA, Altfeld M, Marincola FM, Moore C, Mallal SA, Carrington M, Heckerman D, Allen TM, Mullins JI, Korber BT, Goulder PJR, Walker BD, Brander C. 2006. Control of human immunodeficiency virus replication by cytotoxic T lymphocytes targeting subdominant epitopes. Nat. Immunol. 7:173-178. http://dx.doi.org/10.1038/ni1281.
58. Sabbaj S, Bansal A, Ritter GD, Perkins C, Edwards BH, Gough E, Tang J, Szinger JJ, Korber B, Wilson CM, Kaslow, RA, Mulligan MJ, Goepfert PA. 2003. Cross-reactive CD8+T cell epitopes identified in US adolescent minorities. J. Acquir. Immune Defic. Syndr. 33:426-438. http://dx.doi.org/10.1097/00126334-200308010-00003.
59. Kaufmann DE, Bailey PM, Sidney J, Wagner B, Norris PJ, Johnston MN, Cosimi LA, Addo MM, Lichterfeld M, Altfeld M, Frahm N, Brander C, Sette A, Walker BD, Rosenberg ES. 2004. Comprehensive analysis of human immunodeficiency virus type 1-specific CD4 responses reveals marked immunodominance of gag and nef and the presence of broadly recognized peptides. J. Virol. 78:4463-4477. http://dx.doi.org/10.1128/JVI.78.9.4463-4477.2004.
60. Ranasinghe S, Flanders M, Cutler S, Soghoian DZ, Ghebremichael M, Davis I, Lindqvist M, Pereyra F, Walker BD, Heckerman D, Streeck H. 2012. HIV-specific CD4 T cell responses to different viral proteins have discordant associations with viral load and clinical outcome. J. Virol. 86: 277-283. http://dx.doi.org/10.1128/JVI.05577-11.
61. Kløverpris HN, Harndahl M, Leslie AJ, Carlson JM, Ismail N, van der Stok M, Huang K-HG, Chen F, Riddell L, Steyn D, Goedhals D, van Vuuren C, Frater J, Walker BD, Carrington M, Ndung'u T, Buus S, Goulder P. 2012. HIV control through a single nucleotide on the HLA-B locus. J. Virol. 86:11493-11500. http://dx.doi.org/10.1128/JVI.01020-12.
62. Sunshine J, Kim M, Carlson JM, Heckerman D, Czartoski J, Migueles A, Maenza J, McElrath MJ, Mullins JI, Frahm N. 2014. Increased sequence coverage through combined targeting of variant and conserved epitopes correlates with control of HIV replication. J. Virol. 88:1354-1365. http://dx.doi.org/10.1128/JVI.02361-13.
63. Korber B, Gnanakaran S. 2009. The implications of patterns in HIV diversity for neutralizing antibody induction and susceptibility. Curr. Opin. HIV AIDS 4:408-417. http://dx.doi.org/10.1097/COH.0b013e328 32f129e.
64. Kwong PD, Wyatt R, Robinson J, Sweet RW, Sodroski J, Hendrickson WA. 1998. Structure of an HIV gp120 envelope glycoprotein in complex with the CD4 receptor and a neutralizing human antibody. Nature 393: 648-659. http://dx.doi.org/10.1038/31405.
65. Zhou T, Georgiev I, Wu X, Yang Z-Y, Dai K, Finzi A, Kwon Do Y, Scheid JF, Shi W, Xu L, Yang Y, Zhu J, Nussenzweig MC, Sodroski J, Shapiro L, Nabel GJ, Mascola JR, Kwong PD. 2010. Structural basis for broad and potent neutralization of HIV-1 by antibody VRC01. Science 329:811-817. http://dx.doi.org/10.1126/science.1192819.
66. Kalia V, Sarkar S, Gupta P, Montelaro C, Montelaro RC. 2003. Rational site-directed mutations of the LLP-1 and LLP-2 lentivirus lytic peptide domains in the intracytoplasmic tail of human immunodeficiency virus type 1 gp41 indicate common functions in cell-cell fusion but distinct roles in virion envelope incorporation. J. Virol. 77:3634-3646. http://dx.doi.org/10.1128/JVI.77.6.3634-3646.2003.
67. Lee S-K, Potempa M, Swanstrom R. 2012. The choreography of HIV-1 proteolytic processing and virion assembly. J. Biol. Chem. 287:40867-40874. http://dx.doi.org/10.1074/jbc.R112.399444.
68. Checkley MA, Luttge BG, Soheilian F, Nagashima K, Freed EO. 2010. The capsid-spacer peptide 1 Gag processing intermediate is a dominantnegative inhibitor of HIV-1 maturation. Virology 400:137-144. http://dx.doi.org/10.1016/j.virol.2010.01.028.
69. Goulder PJR, Phillips RE, Colbert RA, McAdam S, Ogg G, Nowak MA, Giangrande P, Luzzi G, Morgana 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.
70. Kelleher AD, Long C, Holmes EC, Allen RL, Wilson J, Conlon C, Workman C, Shaunak S, Olson K, Goulder PJR, Brander C, Ogg G, Sullivan JS, Dyer W, Jones I, McMichael AJ, Rowland-Jones S, Phillips RE. 2001. Clustered mutations in HIV-1 gag are consistently required for escape from HLA-B27-restricted cytotoxic T lymphocyte responses. J. Exp. Med. 193:375-386. http://dx.doi.org/10.1084/jem.193.3.375.
71. Feeney ME, Tang Y, Roosevelt KA, Leslie AJ, Mcintosh K, Karthas N, Walker BD, Goulder PJR. 2004. Immune escape precedes breakthrough human immunodeficiency virus type 1 viremia and broadening of the cytotoxic T-lymphocyte response in an HLA-B27-positive long-termnonprogressing child. J. Virol. 78:8927-8930. http://dx.doi.org/10.1128/JVI.78.16.8927-8930.2004.
72. Ammaranond P, van Bockel DJ, Petoumenos K, McMurchie M, Finlayson R, Middleton MG, Davenport MP, Venturi V, Suzuki K, Gelgor L, Kaldor JM, Cooper DA, Kelleher AD. 2011. HIV immune escape at an immunodominant epitope in HLA-B*27-positive individuals predicts viral load outcome. J. Immunol. 186:479-488. http://dx.doi.org/10.4049/jimmunol.0903227.
73. Crawford H, Lumm W, Leslie AJ, Schaefer M, Boeras D, Prado JG, Tang J, Farmer P, Ndung'u T, Lakhi S, Gilmour J, Goepfert P, Walker BD, Kaslow R, Mulenga J, Allen S, Goulder PJR, Hunter E. 2009. Evolution of HLA-B*5703 HIV-1 escape mutations in HLA-B*5703-positive individuals and their transmission recipients. J. Exp. Med. 206: 909-921. http://dx.doi.org/10.1084/jem.20081984.
74. Ntale RS, Chopera DR, Ngandu NK, Assis de Rosa D, Zembe L, Gamieldien H, Mlotshwa M, Werner L, Woodman Z, Mlisana K, Abdool Karim S, Gray CM, Williamson C. 2012. Temporal association of HLA-B*81:01 and B*39:10 mediated HIV-1 p24 sequence evolution with disease progression. J. Virol. 86:12013-24. http://dx.doi.org/10.1128/JVI.00539-12.
75. Draenert R, Brander C, Yu XG, Altfeld M, Verrill CL, Feeney ME, Walker BD, Goulder PJR. 2004. Impact of intrapeptide epitope location on CD8 T cell recognition: implications for design of overlapping peptide panels. AIDS 18:871. http://dx.doi.org/10.1097/00002030-200404090-00004.
76. Yokomaku Y, Miura H, Tomiyama H, Kawana-Tachikawa A, Takiguchi M, Kojima A, Nagai Y, Iwamoto A, Matsuda Z, Ariyoshi K. 2004. Impaired processing and presentation of cytotoxic-T-lymphocyte (CTL) epitopes are major escape mechanisms from CTL immune pressure in human immunodeficiency virus type 1 infection. J. Virol. 78:1324-1332. http://dx.doi.org/10.1128/JVI.78.3.1324-1332.2004.
77. Zhang SC, Martin E, Shimada M, Godfrey SB, Fricke J, Locastro S, Lai NY, Liebesny P, Carlson JM, Brumme CJ, Ogbechie OA, Chen H, Walker BD, Brumme ZL, Kavanagh DG, Le Gall S. 2012. Aminopeptidase substrate preference affects HIV epitope presentation and predicts immune escape patterns in HIV-infected individuals. J. Immunol. 188: 5924-5934. http://dx.doi.org/10.4049/jimmunol.1200219.
78. Ammaranond P, Zaunders J, Satchell C, van Bockel D, Cooper DA, Kelleher AD. 2005. A new variant cytotoxic T lymphocyte escape mutation in HLA-B27-positive individuals infected with HIV type 1. AIDS Res. Hum. Retroviruses 21:395-397. http://dx.doi.org/10.1089/aid.2005.21.395.
79. Cale EM, Bazick HS, Rianprakaisang TA, Alam SM, Letvin NL. 2011. Mutations in a dominant Nef epitope of simian immunodeficiency virus diminish TCR:epitope peptide affinity but not epitope peptide: MHC class I binding. J. Immunol. 187:3300-3313. http://dx.doi.org/10.4049/jimmunol.1101080.
80. Theodossis A, Guillonneau C, Welland A, Ely LK, Clements CS, Williamson NA, Webb AI, Wilce Ja Mulder RJ, Dunstone MA, Doherty PC, McCluskey J, Purcell AW, Turner SJ, Rossjohn J. 2010. Constraints within major histocompatibility complex class I restricted peptides: presentation and consequences for T-cell recognition. Proc. Natl. Acad. Sci. U. S. A. 107:5534-5539. http://dx.doi.org/10.1073/pnas.1000032107.
81. Iversen AKN, Stewart-Jones G, Learn GH, Christie N, Sylvester-Hviid C, Armitage AE, Kaul R, Beattie T, Lee JK, Li Y, Chotiyarnwong P, Dong T, Xu X, Luscher MA, MacDonald K, Ullum H, Klarlund-Pedersen B, Skinhøj P, Fugger L, Buus S, Mullins JI, Jones EY, van der Merwe PA, McMichael AJ. 2006. Conflicting selective forces affect T cell receptor contacts in an immunodominant human immunodeficiency virus epitope. Nat. Immunol. 7:179-189. http://dx.doi.org/10.1038/ni1298.
82. Iglesias MC, Almeida JR, Fastenackels S, van Bockel DJ, Hashimoto M, Venturi V, Gostick E, Urrutia A, Wooldridge L, Clement M, Gras S, Wilmann PG, Autran B, Moris A, Rossjohn J, Davenport MP, Takiguchi M, Brander C, Douek DC, Kelleher AD, Price DA, Appay V. 2011. Escape from highly effective public CD8+ T-cell clonotypes by HIV. Blood 118:2138-2149. http://dx.doi.org/10.1182/blood-2011-01-328781.
83. Carlson JM, Listgarten J, Pfeifer N, Tan V, Kadie C, Walker BD, Ndung'u T, Shapiro R, Frater J, Brumme ZL, Goulder PJR, Heckerman D. 2012. Widespread impact of HLA restriction on immune control and escape pathways of HIV-1. J. Virol. 86:5230-5243. http://dx.doi.org/10.1128/JVI.06728-11.
84. Brumme ZL, Brumme CJ, Heckerman D, Korber BT, Daniels M, Carlson JM, Kadie C, Bhattacharya T, Chui C, Szinger J, Mo T, Hogg RS, Montaner JSG, Frahm N, Brander C, Walker BD, Harrigan PR. 2007. Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1. PLoS Pathog. 3:e94. http://dx.doi.org/10.1371/journal.ppat.0030094.
85. Bartha I, Carlson JM, Brumme CJ, McLaren PJ, Brumme ZL, John M, Haas DW, Martinez-Picado J, Dalmau J, López-Galíndez C, Casado C, Rauch A, Günthard HF, Bernasconi E, Vernazza P, Klimkait T, Yerly S, O'Brien SJ, Listgarten J, Pfeifer N, Lippert C, Fusi N, Kutalik Z, Allen TM, Müller V, Harrigan PR, Heckerman D, Telenti A, Fellay J. 2013. A genome-to-genome analysis of associations between human genetic variation, HIV-1 sequence diversity, and viral control. eLife 2:e01123. http://dx.doi.org/10.7554/eLife.01123.
86. Brumme ZL, Brumme CJ, Carlson JM, 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 SA, Altfeld M, Heckerman D, Walker BD. 2008. Marked epitope-and allelespecific 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.
87. Brockman MA, Schneidewind A, Lahaie M, Schmidt A, Miura T, Desouza I, Ryvkin F, Derdeyn CA, Allen S, Hunter E, Mulenga J, Goepfert PA, Walker BD, Allen TM. 2007. Escape and compensation from early HLA-B57-mediated cytotoxic T-lymphocyte pressure on human immunodeficiency virus type 1 Gag alter capsid interactions with cyclophilin A. J. Virol. 81:12608-12618. http://dx.doi.org/10.1128/JVI.01369-07.
88. Schneidewind A, Brumme ZL, Brumme CJ, Power KA, Reyor LL, O'Sullivan K, Gladden A, Hempel U, Kuntzen T, Wang YE, Oniangue-Ndza C, Jessen H, Markowitz M, Rosenberg ES, Sékaly R-P, Kelleher AD, Walker BD, Allen TM. 2009. Transmission and long-term stability of compensated CD8 escape mutations. J. Virol. 83:3993-3997. http://dx.doi.org/10.1128/JVI.01108-08.
89. Ndhlovu ZM, Proudfoot J, Cesa K, Alvino DM, McMullen A, Vine S, Stampouloglou E, Piechocka-Trocha A, Walker BD, Pereyra F. 2012. Elite controllers with low to absent effector CD8+ 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.
90. Borthwick N, Ahmed T, Ondondo B, Hayes P, Rose A, Ebrahimsa U, Hayton E-J, Black A, Bridgeman A, Rosario M, Hill AV, Berrie E, Moyle S, Frahm N, Cox J, Colloca S, Nicosia A, Gilmour J, McMichael AJ, Dorrell L, Hanke T. 2014. Vaccine-elicited human T cells recognizing conserved protein regions inhibit HIV-1. Mol. Ther. 22:464-475. http://dx.doi.org/10.1038/mt.2013.248.
91. + T-cell responses during chronic untreated HIV-1 infection by immunization with subdominant cytotoxic T-lymphocyte epitopes. AIDS 23:1329-1340. http://dx.doi.org/10.1097/QAD.0b013e32832d9b00.