Immune Activation Promotes Evolutionary Conservation of T-Cell Epitopes in HIV-1

PLoS Biology

Volumn 11, Issue 4, 2013, Pages

  Sanjuán, Rafael ^a,b   Nebot, Miguel R ^c   Peris, Joan B ^a   Alcamí, José ^d  

^a UNIVERSITY OF VALENCIA   (Spain)

^b UNIVERSITY OF VALENCIA   (Spain)

^c CSIC   (Spain)

^d INSTITUTO DE SALUD CARLOS III   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

CD4 ANTIGEN; EPITOPE; GAG PROTEIN; NEF PROTEIN; NONSTRUCTURAL PROTEIN 3; NONSTRUCTURAL PROTEIN 4B; NONSTRUCTURAL PROTEIN 5B; POL PROTEIN; VIRUS ENVELOPE PROTEIN; VIRUS PROTEIN;

AMINO ACID SUBSTITUTION; ARTICLE; CD4+ T LYMPHOCYTE; CELL SELECTION; CYTOTOXIC T LYMPHOCYTE; GENETIC CONSERVATION; HELPER CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNE RESPONSE; IMMUNOSTIMULATION; LYMPH NODE; MATHEMATICAL MODEL; MOLECULAR RECOGNITION; PREDICTION; T LYMPHOCYTE ACTIVATION; VIRUS CELL INTERACTION; VIRUS REPLICATION;

ALGORITHMS; AMINO ACID SEQUENCE; COMPUTER SIMULATION; CONSERVED SEQUENCE; EPITOPES, T-LYMPHOCYTE; EVOLUTION, MOLECULAR; GENETIC VARIATION; HIV ANTIGENS; HIV INFECTIONS; HIV-1; HOST-PATHOGEN INTERACTIONS; HUMANS; IMMUNE EVASION; IMMUNITY, CELLULAR; MODELS, GENETIC; VIRAL LOAD; VIRUS REPLICATION;

HUMAN IMMUNODEFICIENCY VIRUS 1; RNA VIRUSES;

EID: 84876966654     PISSN: 15449173     EISSN: 15457885     Source Type: Journal    
DOI: 10.1371/journal.pbio.1001523     Document Type: Article

References (107)

1. Kawashima Y, Pfafferott K, Frater J, Matthews P, Payne R, et al. (2009) Adaptation of HIV-1 to human leukocyte antigen class I. Nature 458: 641-645.
2. Wei X, Decker JM, Wang S, Hui H, Kappes JC, et al. (2003) Antibody neutralization and escape by HIV-1. Nature 422: 307-312.
3. 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: 6103-6110.
4. Frahm N, Korber BT, Adams CM, Szinger JJ, Draenert R, et al. (2004) Consistent cytotoxic-T-lymphocyte targeting of immunodominant regions in human immunodeficiency virus across multiple ethnicities. J Virol 78: 2187-2200.
5. Koup RA, Safrit JT, Cao Y, Andrews CA, McLeod G, et al. (1994) Temporal association of cellular immune responses with the initial control of viremia in primary human immunodeficiency virus type 1 syndrome. J Virol 68: 4650-4655.
6. Ogg GS, Jin X, Bonhoeffer S, Dunbar PR, Nowak MA, et al. (1998) Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279: 2103-2106.
7. Potter SJ, Lacabaratz C, Lambotte O, Perez-Patrigeon S, Vingert B, et al. (2007) Preserved central memory and activated effector memory CD4+ T-cell subsets in human immunodeficiency virus controllers: an ANRS EP36 study. J Virol 81: 13904-13915.
8. Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, et al. (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283: 857-860.
9. Vingert B, Perez-Patrigeon S, Jeannin P, Lambotte O, Boufassa F, et al. (2010) HIV controller CD4+ T cells respond to minimal amounts of Gag antigen due to high TCR avidity. PLoS Pathog 6: e1000780 doi:10.1371/journal.pone.0055570.
10. Wang YE, Li B, Carlson JM, Streeck H, Gladden AD, et al. (2009) Protective HLA class I alleles that restrict acute-phase CD8+ T-cell responses are associated with viral escape mutations located in highly conserved regions of human immunodeficiency virus type 1. J Virol 83: 1845-1855.
11. Carrington M, O'Brien SJ, (2003) The influence of HLA genotype on AIDS. Annu Rev Med 54: 535-551.
12. Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G, et al. (1997) Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 3: 212-217.
13. Goulder PJ, Watkins DI, (2008) Impact of MHC class I diversity on immune control of immunodeficiency virus replication. Nat Rev Immunol 8: 619-630.
14. Korber BT, Letvin NL, Haynes BF, (2009) T-cell vaccine strategies for human immunodeficiency virus, the virus with a thousand faces. J Virol 83: 8300-8314.
15. Allen TM, Altfeld M, Geer SC, Kalife ET, Moore C, et al. (2005) Selective escape from CD8+ T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution. J Virol 79: 13239-13249.
16. Bernardin F, Kong D, Peddada L, Baxter-Lowe LA, Delwart E, (2005) Human immunodeficiency virus mutations during the first month of infection are preferentially found in known cytotoxic T-lymphocyte epitopes. J Virol 79: 11523-11528.
17. Brumme ZL, Brumme CJ, Heckerman D, Korber BT, Daniels M, et al. (2007) Evidence of differential HLA class I-mediated viral evolution in functional and accessory/regulatory genes of HIV-1. PLoS Pathog 3: e94 doi:10.1371/journal.ppat.0030121.
18. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, et al. (2004) Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432: 769-775.
19. Berger EA, Murphy PM, Farber JM, (1999) Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu Rev Immunol 17: 657-700.
20. Addo MM, Yu XG, Rathod A, Cohen D, Eldridge RL, et al. (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.
21. Peters HO, Mendoza MG, Capina RE, Luo M, Mao X, et al. (2008) An integrative bioinformatic approach for studying escape mutations in human immunodeficiency virus type 1 gag in the Pumwani Sex Worker Cohort. J Virol 82: 1980-1992.
22. Rodríguez WR, Addo MM, Rathod A, Fitzpatrick CA, Yu XG, et al. (2004) CD8+ T lymphocyte responses target functionally important regions of Protease and Integrase in HIV-1 infected subjects. J Transl Med 2: 15.
23. Yusim K, Kesmir C, Gaschen B, Addo MM, Altfeld M, et al. (2002) Clustering patterns of cytotoxic T-lymphocyte epitopes in human immunodeficiency virus type 1 (HIV-1) proteins reveal imprints of immune evasion on HIV-1 global variation. J Virol 76: 8757-8768.
24. Seibert SA, Howell CY, Hughes MK, Hughes AL, (1995) Natural selection on the gag, pol, and env genes of human immunodeficiency virus 1 (HIV-1). Mol Biol Evol 12: 803-813.
25. Fontaine Costa AI, Rao X, Lechenadec E, van Baarle D, Kesmir C, (2010) HLA-B molecules target more conserved regions of the HIV-1 proteome. AIDS 24: 211-215.
26. Irausquin SJ, Hughes AL, (2011) Conflicting selection pressures on T-cell epitopes in HIV-1 subtype B. Infect Genet Evol 11: 483-488.
27. Snoeck J, Fellay J, Bartha I, Douek DC, Telenti A, (2011) Mapping of positive selection sites in the HIV-1 genome in the context of RNA and protein structural constraints. Retrovirology 8: 87.
28. Altfeld M, Addo MM, Shankarappa R, Lee PK, Allen TM, et al. (2003) Enhanced detection of human immunodeficiency virus type 1-specific T-cell responses to highly variable regions by using peptides based on autologous virus sequences. J Virol 77: 7330-7340.
29. Lucchiari-Hartz M, Lindo V, Hitziger N, Gaedicke S, Saveanu L, et al. (2003) Differential proteasomal processing of hydrophobic and hydrophilic protein regions: contribution to cytotoxic T lymphocyte epitope clustering in HIV-1-Nef. Proc Natl Acad Sci USA 100: 7755-7760.
30. Woo J, Robertson DL, Lovell SC, (2010) Constraints on HIV-1 diversity from protein structure. J Virol 84: 12995-13003.
31. McMichael A, Klenerman P, (2002) HIV/AIDS. HLA leaves its footprints on HIV. Science 296: 1410-1411.
32. Schmid BV, Kesmir C, de Boer RJ, (2008) The specificity and polymorphism of the MHC class I prevents the global adaptation of HIV-1 to the monomorphic proteasome and TAP. PLoS ONE 3: e3525 doi:10.1371/journal.pone.0003525.
33. Grenfell BT, Pybus OG, Gog JR, Wood JL, Daly JM, et al. (2004) Unifying the epidemiological and evolutionary dynamics of pathogens. Science 303: 327-332.
34. Twiddy SS, Woelk CH, Holmes EC, (2002) Phylogenetic evidence for adaptive evolution of dengue viruses in nature. J Gen Virol 83: 1679-1689.
35. Ina Y, Gojobori T, (1994) Statistical analysis of nucleotide sequences of the hemagglutinin gene of human influenza A viruses. Proc Natl Acad Sci USA 91: 8388-8392.
36. Bhatt S, Holmes EC, Pybus OG, (2011) The genomic rate of molecular adaptation of the human influenza A virus. Mol Biol Evol 28: 2443-2451.
37. Ruhl M, Knuschke T, Schewior K, Glavinic L, Neumann-Haefelin C, et al. (2011) CD8+ T-cell response promotes evolution of hepatitis C virus nonstructural proteins. Gastroenterology 140: 2064-2073.
38. Grossman Z, Meier-Schellersheim M, Sousa AE, Victorino RM, Paul WE, (2002) CD4+ T-cell depletion in HIV infection: are we closer to understanding the cause? Nat Med 8: 319-323.
39. Brenchley JM, Silvestri G, Douek DC, (2010) Nonprogressive and progressive primate immunodeficiency lentivirus infections. Immunity 32: 737-742.
40. Choudhary SK, Vrisekoop N, Jansen CA, Otto SA, Schuitemaker H, et al. (2007) Low immune activation despite high levels of pathogenic human immunodeficiency virus type 1 results in long-term asymptomatic disease. J Virol 81: 8838-8842.
41. Klatt NR, Villinger F, Bostik P, Gordon SN, Pereira L, et al. (2008) Availability of activated CD4+ T cells dictates the level of viremia in naturally SIV-infected sooty mangabeys. J Clin Invest 118: 2039-2049.
42. Stevenson M, Stanwick TL, Dempsey MP, Lamonica CA, (1990) HIV-1 replication is controlled at the level of T cell activation and proviral integration. EMBO J 9: 1551-1560.
43. Varmus HE, Padgett T, Heasley S, Simon G, Bishop JM, (1977) Cellular functions are required for the synthesis and integration of avian sarcoma virus-specific DNA. Cell 11: 307-319.
44. Coiras M, López-Huertas MR, Pérez-Olmeda M, Alcamí J, (2009) Understanding HIV-1 latency provides clues for the eradication of long-term reservoirs. Nat Rev Microbiol 7: 798-812.
45. Zack JA, Arrigo SJ, Weitsman SR, Go AS, Haislip A, et al. (1990) HIV-1 entry into quiescent primary lymphocytes: molecular analysis reveals a labile, latent viral structure. Cell 61: 213-222.
46. Zack JA, Haislip AM, Krogstad P, Chen IS, (1992) Incompletely reverse-transcribed human immunodeficiency virus type 1 genomes in quiescent cells can function as intermediates in the retroviral life cycle. J Virol 66: 1717-1725.
47. Zhang ZQ, Wietgrefe SW, Li Q, Shore MD, Duan L, et al. (2004) Roles of substrate availability and infection of resting and activated CD4+ T cells in transmission and acute simian immunodeficiency virus infection. Proc Natl Acad Sci USA 101: 5640-5645.
48. Tsegaye TS, Pohlmann S, (2010) The multiple facets of HIV attachment to dendritic cell lectins. Cell Microbiol 12: 1553-1561.
49. Wu L, KewalRamani VN, (2006) Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol 6: 859-868.
50. Asquith B, Edwards CT, Lipsitch M, McLean AR, (2006) Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. PLoS Biol 4: e90 doi:10.1371/journal.pbio.0040090.
51. Ganusov VV, Goonetilleke N, Liu MK, Ferrari G, Shaw GM, et al. (2011) Fitness costs and diversity of the cytotoxic T lymphocyte (CTL) response determine the rate of CTL escape during acute and chronic phases of HIV infection. J Virol 85: 10518-10528.
52. Goonetilleke N, Liu MK, Salazar-González JF, Ferrari G, Giorgi E, et al. (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: 1253-1272.
53. Paul S, Piontkivska H, (2010) Frequent associations between CTL and T-Helper epitopes in HIV-1 genomes and implications for multi-epitope vaccine designs. BMC Microbiol 10: 212.
54. Watts JM, Dang KK, Gorelick RJ, Leonard CW, Bess JW Jr, et al. (2009) Architecture and secondary structure of an entire HIV-1 RNA genome. Nature 460: 711-716.
55. Abrahams MR, Anderson JA, Giorgi EE, Seoighe C, Mlisana K, et al. (2009) Quantitating the multiplicity of infection with human immunodeficiency virus type 1 subtype C reveals a non-poisson distribution of transmitted variants. J Virol 83: 3556-3567.
56. Haaland RE, Hawkins PA, Salazar-González J, Johnson A, Tichacek A, et al. (2009) Inflammatory genital infections mitigate a severe genetic bottleneck in heterosexual transmission of subtype A and C HIV-1. PLoS Pathog 5: e1000274 doi:10.1371/journal.ppat.1000274.
57. Keele BF, Giorgi EE, Salazar-González JF, Decker JM, Pham KT, et al. (2008) Identification and characterization of transmitted and early founder virus envelopes in primary HIV-1 infection. Proc Natl Acad Sci USA 105: 7552-7557.
58. Cox AL, Mosbruger T, Mao Q, Liu Z, Wang XH, et al. (2005) Cellular immune selection with hepatitis C virus persistence in humans. J Exp Med 201: 1741-1752.
59. Erickson AL, Kimura Y, Igarashi S, Eichelberger J, Houghton M, et al. (2001) The outcome of hepatitis C virus infection is predicted by escape mutations in epitopes targeted by cytotoxic T lymphocytes. Immunity 15: 883-895.
60. Gaudieri S, Rauch A, Park LP, Freitas E, Herrmann S, et al. (2006) Evidence of viral adaptation to HLA class I-restricted immune pressure in chronic hepatitis C virus infection. J Virol 80: 11094-11104.
61. Merani S, Petrovic D, James I, Chopra A, Cooper D, et al. (2011) Effect of immune pressure on hepatitis C virus evolution: insights from a single-source outbreak. Hepatology 53: 396-405.
62. Rauch A, James I, Pfafferott K, Nolan D, Klenerman P, et al. (2009) Divergent adaptation of hepatitis C virus genotypes 1 and 3 to human leukocyte antigen-restricted immune pressure. Hepatology 50: 1017-1029.
63. Wolfl M, Rutebemberwa A, Mosbruger T, Mao Q, Li HM, et al. (2008) Hepatitis C virus immune escape via exploitation of a hole in the T cell repertoire. J Immunol 181: 6435-6446.
64. McIlroy D, Autran B, Cheynier R, Wain-Hobson S, Clauvel JP, et al. (1995) Infection frequency of dendritic cells and CD4+ T lymphocytes in spleens of human immunodeficiency virus-positive patients. J Virol 69: 4737-4745.
65. Douek DC, Brenchley JM, Betts MR, Ambrozak DR, Hill BJ, et al. (2002) HIV preferentially infects HIV-specific CD4+ T cells. Nature 417: 95-98.
66. Brenchley JM, Ruff LE, Casazza JP, Koup RA, Price DA, et al. (2006) Preferential infection shortens the life span of human immunodeficiency virus-specific CD4+ T cells in vivo. J Virol 80: 6801-6809.
67. Althaus CL, de Boer RJ, (2008) Dynamics of immune escape during HIV/SIV infection. PLoS Comput Biol 4: e1000103 doi:10.1371/journal.pcbi.1000103.
68. Fraser C, Ferguson NM, de Wolf F, Anderson RM, (2001) The role of antigenic stimulation and cytotoxic T cell activity in regulating the long-term immunopathogenesis of HIV: mechanisms and clinical implications. Proc Biol Sci 268: 2085-2095.
69. Nowak MA, Anderson RM, McLean AR, Wolfs TF, Goudsmit J, et al. (1991) Antigenic diversity thresholds and the development of AIDS. Science 254: 963-969.
70. Macallan DC, Asquith B, Irvine AJ, Wallace DL, Worth A, et al. (2003) Measurement and modeling of human T cell kinetics. Eur J Immunol 33: 2316-2326.
71. Bofill M, Janossy G, Lee CA, MacDonald-Burns D, Phillips AN, et al. (1992) Laboratory control values for CD4 and CD8 T lymphocytes. Implications for HIV-1 diagnosis. Clin Exp Immunol 88: 243-252.
72. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, et al. (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373: 123-126.
73. Markowitz M, Louie M, Hurley A, Sun E, Di MM, et al. (2003) A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. J Virol 77: 5037-5038.
74. Perelson AS, Neumann AU, Markowitz M, Leonard JM, Ho DD, (1996) HIV-1 dynamics in vivo: virion clearance rate, infected cell life-span, and viral generation time. Science 271: 1582-1586.
75. Rodrigo AG, Shpaer EG, Delwart EL, Iversen AK, Gallo MV, et al. (1999) Coalescent estimates of HIV-1 generation time in vivo. Proc Natl Acad Sci USA 96: 2187-2191.
76. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, et al. (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373: 117-122.
77. Althaus CL, De Vos AS, de Boer RJ, (2009) Reassessing the human immunodeficiency virus type 1 life cycle through age-structured modeling: life span of infected cells, viral generation time, and basic reproductive number, R0. J Virol 83: 7659-7667.
78. Chen HY, Di MM, Perelson AS, Ho DD, et al. (2007) Determination of virus burst size in vivo using a single-cycle SIV in rhesus macaques. Proc Natl Acad Sci USA 104: 19079-19084.
79. De Boer RJ, Ribeiro RM, Perelson AS, (2010) Current estimates for HIV-1 production imply rapid viral clearance in lymphoid tissues. PLoS Comput Biol 6: e1000906 doi:10.1371/journal.pcbi.1000906.
80. Hockett RD, Kilby JM, Derdeyn CA, Saag MS, Sillers M, et al. (1999) Constant mean viral copy number per infected cell in tissues regardless of high, low, or undetectable plasma HIV RNA. J Exp Med 189: 1545-1554.
81. Reilly C, Wietgrefe S, Sedgewick G, Haase A, (2007) Determination of simian immunodeficiency virus production by infected activated and resting cells. AIDS 21: 163-168.
82. Ramratnam B, Bonhoeffer S, Binley J, Hurley A, Zhang L, et al. (1999) Rapid production and clearance of HIV-1 and hepatitis C virus assessed by large volume plasma apheresis. Lancet 354: 1782-1785.
83. Sanjuán R, Nebot MR, Chirico N, Mansky LM, Belshaw R, (2010) Viral mutation rates. J Virol 84: 9733-9748.
84. Fraser C, Hollingsworth TD, Chapman R, de WF, Hanage WP, (2007) Variation in HIV-1 set-point viral load: epidemiological analysis and an evolutionary hypothesis. Proc Natl Acad Sci USA 104: 17441-17446.
85. Martínez-Picado J, Prado JG, Fry EE, Pfafferott K, Leslie A, et al. (2006) Fitness cost of escape mutations in p24 Gag in association with control of human immunodeficiency virus type 1. J Virol 80: 3617-3623.
86. Schneidewind A, Brockman MA, Yang R, Adam RI, Li B, et al. (2007) Escape from the dominant HLA-B27-restricted cytotoxic T-lymphocyte response in Gag is associated with a dramatic reduction in human immunodeficiency virus type 1 replication. J Virol 81: 12382-12393.
87. Wright JK, Brumme ZL, Carlson JM, Heckerman D, Kadie CM, et al. (2010) Gag-protease-mediated replication capacity in HIV-1 subtype C chronic infection: associations with HLA type and clinical parameters. J Virol 84: 10820-10831.
88. Liu Y, McNevin J, Zhao H, Tebit DM, Troyer RM, et al. (2007) Evolution of human immunodeficiency virus type 1 cytotoxic T-lymphocyte epitopes: fitness-balanced escape. J Virol 81: 12179-12188.
89. Matthews PC, Prendergast A, Leslie A, Crawford H, Payne R, et al. (2008) Central role of reverting mutations in HLA associations with human immunodeficiency virus set point. J Virol 82: 8548-8559.
90. Schneidewind A, Brockman MA, Sidney J, Wang YE, Chen H, et al. (2008) Structural and functional constraints limit options for cytotoxic T-lymphocyte escape in the immunodominant HLA-B27-restricted epitope in human immunodeficiency virus type 1 capsid. J Virol 82: 5594-5605.
91. Troyer RM, McNevin J, Liu Y, Zhang SC, Krizan RW, et al. (2009) Variable fitness impact of HIV-1 escape mutations to cytotoxic T lymphocyte (CTL) response. PLoS Pathog 5: e1000365 doi:10.1371/journal.ppat.1000365.
92. Elena SF, Sanjuán R, (2007) Virus evolution: insights from an experimental approach. Ann Rev Ecol Sys Evol 38: 27-52.
93. Moore CB, John M, James IR, Christiansen FT, Witt CS, et al. (2002) Evidence of HIV-1 adaptation to HLA-restricted immune responses at a population level. Science 296: 1439-1443.
94. Koibuchi T, Allen TM, Lichterfeld M, Mui SK, O'Sullivan KM, et al. (2005) Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection. J Virol 79: 8171-8181.
95. Li Q, Duan L, Estes JD, Ma ZM, Rourke T, et al. (2005) Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 434: 1148-1152.
96. Mattapallil JJ, Douek DC, Hill B, Nishimura Y, Martin M, et al. (2005) Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection. Nature 434: 1093-1097.
97. Zhang Z, Schuler T, Zupancic M, Wietgrefe S, Staskus KA, et al. (1999) Sexual transmission and propagation of SIV and HIV in resting and activated CD4+ T cells. Science 286: 1353-1357.
98. Lichterfeld M, Yu XG, Le GS, Altfeld M, (2005) Immunodominance of HIV-1-specific CD8(+) T-cell responses in acute HIV-1 infection: at the crossroads of viral and host genetics. Trends Immunol 26: 166-171.
99. Corey L, McElrath MJ, Kublin JG, (2009) Post-step modifications for research on HIV vaccines. AIDS 23: 3-8.
100. McElrath MJ, De Rosa SC, Moodie Z, Dubey S, Kierstead L, et al. (2008) HIV-1 vaccine-induced immunity in the test-of-concept Step Study: a case-cohort analysis. Lancet 372: 1894-1905.
101. Comas I, Chakravartti J, Small PM, Galagan J, Niemann S, et al. (2010) Human T cell epitopes of Mycobacterium tuberculosis are evolutionarily hyperconserved. Nat Genet 42: 498-503.
102. Geldmacher C, Schuetz A, Ngwenyama N, Casazza JP, Sanga E, et al. (2008) Early depletion of Mycobacterium tuberculosis-specific T helper 1 cell responses after HIV-1 infection. J Infect Dis 198: 1590-1598.
103. Geldmacher C, Ngwenyama N, Schuetz A, Petrovas C, Reither K, et al. (2010) Preferential infection and depletion of Mycobacterium tuberculosis-specific CD4 T cells after HIV-1 infection. J Exp Med 207: 2869-2881.
104. Kosakovsky Pond SL, Posada D, Gravenor MB, Woelk CH, Frost SD, (2006) Automated phylogenetic detection of recombination using a genetic algorithm. Mol Biol Evol 23: 1891-1901.
105. Kosakovsky Pond SL, Frost SD, (2005) Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol 22: 1208-1222.
106. Pond SL, Frost SD, Muse SV, (2005) HyPhy: hypothesis testing using phylogenies. Bioinformatics 21: 676-679.
107. Koibuchi T, Allen TM, Lichterfeld M, Mui SK, O'Sullivan KM, et al. (2005) Limited sequence evolution within persistently targeted CD8 epitopes in chronic human immunodeficiency virus type 1 infection. J Virol 79: 8171-8181.