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Science 24 May 2002:
Vol. 296. no. 5572, pp. 1439 - 1443
DOI: 10.1126/science.1069660
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Research Articles

Evidence of HIV-1 Adaptation to HLA-Restricted Immune Responses at a Population Level

Corey B. Moore,1 Mina John,12 Ian R. James,1 Frank T. Christiansen,23 Campbell S. Witt,12 Simon A. Mallal12*

Antigen-specific T cell immunity is HLA-restricted. Human immunodeficiency virus-type 1 (HIV-1) mutations that allow escape from host immune responses may therefore be HLA allele-specific. We analyzed HIV-1 reverse transcriptase sequences from a large HLA-diverse population of HIV-1-infected individuals. Polymorphisms in HIV-1 were most evident at sites of least functional or structural constraint and frequently were associated with particular host HLA class I alleles. Absence of polymorphism was also HLA allele-specific. At a population level, the degree of HLA-associated selection in viral sequence was predictive of viral load. These results support a fundamental role for HLA-restricted immune responses in driving and shaping HIV-1 evolution in vivo.

1 Centre for Clinical Immunology and Biomedical Statistics, Royal Perth Hospital and Murdoch University, Level 2 North Block, Royal Perth Hospital, Wellington Street, WA 6000, Australia.
2 Department of Clinical Immunology and Biochemical Genetics, Royal Perth Hospital.
3 Department of Pathology, University of Western Australia, WA 6009, Australia.
*   To whom correspondence should be addressed. E-mail: mallal{at}prodigal.murdoch.edu.au

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T. M. Allen, M. Altfeld, X. G. Yu, K. M. O'Sullivan, M. Lichterfeld, S. Le Gall, M. John, B. R. Mothe, P. K. Lee, E. T. Kalife, et al. (2004)
J. Virol. 78, 7069-7078
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Antiretroviral Drug Resistance Mutations Sustain or Enhance CTL Recognition of Common HIV-1 Pol Epitopes.
R. D. Mason, M. I. Bowmer, C. M. Howley, M. Gallant, J. C. E. Myers, and M. D. Grant (2004)
J. Immunol. 172, 7212-7219
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Migration of Antigen-Specific T Cells Away from CXCR4-Binding Human Immunodeficiency Virus Type 1 gp120.
D. M. Brainard, W. G. Tharp, E. Granado, N. Miller, A. K. Trocha, X.-H. Ren, B. Conrad, E. F. Terwilliger, R. Wyatt, B. D. Walker, et al. (2004)
J. Virol. 78, 5184-5193
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Immune Selection for Altered Antigen Processing Leads to Cytotoxic T Lymphocyte Escape in Chronic HIV-1 Infection.
R. Draenert, S. Le Gall, K. J. Pfafferott, A. J. Leslie, P. Chetty, C. Brander, E. C. Holmes, S.-C. Chang, M. E. Feeney, M. M. Addo, et al. (2004)
J. Exp. Med. 199, 905-915
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Positive Selection Detection in 40,000 Human Immunodeficiency Virus (HIV) Type 1 Sequences Automatically Identifies Drug Resistance and Positive Fitness Mutations in HIV Protease and Reverse Transcriptase.
L. Chen, A. Perlina, and C. J. Lee (2004)
J. Virol. 78, 3722-3732
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Consistent Cytotoxic-T-Lymphocyte Targeting of Immunodominant Regions in Human Immunodeficiency Virus across Multiple Ethnicities.
N. Frahm, B. T. Korber, C. M. Adams, J. J. Szinger, R. Draenert, M. M. Addo, M. E. Feeney, K. Yusim, K. Sango, N. V. Brown, et al. (2004)
J. Virol. 78, 2187-2200
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Mapping a locus for susceptibility to HIV-1-associated nephropathy to mouse chromosome 3.
A. G. Gharavi, T. Ahmad, R. D. Wong, R. Hooshyar, J. Vaughn, S. Oller, R. Z. Frankel, L. A. Bruggeman, V. D. D'Agati, P. E. Klotman, et al. (2004)
PNAS 101, 2488-2493
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Comparative Study of Adaptive Molecular Evolution in Different Human Immunodeficiency Virus Groups and Subtypes.
M. Choisy, C. H. Woelk, J.-F. Guegan, and D. L. Robertson (2004)
J. Virol. 78, 1962-1970
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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.
Y. Yokomaku, H. Miura, H. Tomiyama, A. Kawana-Tachikawa, M. Takiguchi, A. Kojima, Y. Nagai, A. Iwamoto, Z. Matsuda, and K. Ariyoshi (2004)
J. Virol. 78, 1324-1332
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