Adaptation of HIV-1 to human leukocyte antigen class I

• Published in: Nature 2009-04, Vol.458 (7238), p.641-645
• Main Authors: Kawashima, Yuka, Pfafferott, Katja, Frater, John, Matthews, Philippa, Payne, Rebecca, Addo, Marylyn, Gatanaga, Hiroyuki, Fujiwara, Mamoru, Hachiya, Atsuko, Koizumi, Hirokazu, Kuse, Nozomi, Oka, Shinichi, Duda, Anna, Prendergast, Andrew, Crawford, Hayley, Leslie, Alasdair, Brumme, Zabrina, Brumme, Chanson, Allen, Todd, Brander, Christian, Kaslow, Richard, Tang, James, Hunter, Eric, Allen, Susan, Mulenga, Joseph, Branch, Songee, Roach, Tim, John, Mina, Mallal, Simon, Ogwu, Anthony, Shapiro, Roger, Prado, Julia G., Fidler, Sarah, Weber, Jonathan, Pybus, Oliver G., Klenerman, Paul, Ndung’u, Thumbi, Phillips, Rodney, Heckerman, David, Harrigan, P. Richard, Walker, Bruce D., Takiguchi, Masafumi, Goulder, Philip
• Format: Article
• Language: English
• Subjects: Alleles; Analysis; Antigen receptors, T cell; Antigens; Biological and medical sciences; CD8-Positive T-Lymphocytes - immunology; Cohort Studies; Epitopes, T-Lymphocyte - chemistry; Epitopes, T-Lymphocyte - genetics; Epitopes, T-Lymphocyte - immunology; gag Gene Products, Human Immunodeficiency Virus - chemistry; gag Gene Products, Human Immunodeficiency Virus - genetics; gag Gene Products, Human Immunodeficiency Virus - immunology; Histocompatibility antigens; HIV; HIV antigens; HIV Antigens - chemistry; HIV Antigens - genetics; HIV Antigens - immunology; HIV-1 - genetics; HIV-1 - immunology; HIV-1 - physiology; HLA histocompatibility antigens; HLA-B Antigens - genetics; HLA-B Antigens - immunology; Human immunodeficiency virus; Human immunodeficiency virus 1; Human viral diseases; Humanities and Social Sciences; Humans; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Infectious diseases; Internationality; letter; Leukocytes; Leukocytes - immunology; Medical research; Medical sciences; multidisciplinary; Mutation; Polymorphism, Genetic; Receptors; Science; Science (multidisciplinary); T cells; Viral diseases; Viral diseases of the lymphoid tissue and the blood. Aids
• ISSN: 0028-0836; 1476-4687; 1476-4687; 1476-4679
• DOI: 10.1038/nature07746

HIV a moving target In order to determine whether HIV is adapting to the human leukocyte antigen (HLA) alleles, such as HLA-B * 57, B * 57 and B * 51, that mediate successful control of the virus, viral sequences and HLA types were analysed in more than 500 HIV-infected subjects drawn from North America, the Caribbean, Europe, Africa, Australasia and Asia. The results reveal that HIV is evolving at the population level in response to immune selection pressure. Whilst this does not indicate that HIV is necessarily 'winning' the evolutionary struggle against humans, it does suggest that successful HIV vaccines — like those against influenza — will need to keep pace with a changing immunological landscape. This paper traces the adaptation of HIV to HLA alleles in 2,500 HIV-infected subjects and demonstrates a strong correlation between the prevalence of escape mutations within well characterized epitopes and the prevalence of the respective HLA alleles, thereby providing evidence that the virus is indeed adapting to effective immune responses. The rapid and extensive spread of the human immunodeficiency virus (HIV) epidemic provides a rare opportunity to witness host–pathogen co-evolution involving humans. A focal point is the interaction between genes encoding human leukocyte antigen (HLA) and those encoding HIV proteins. HLA molecules present fragments (epitopes) of HIV proteins on the surface of infected cells to enable immune recognition and killing by CD8 + T cells; particular HLA molecules, such as HLA-B*57, HLA-B*27 and HLA-B*51, are more likely to mediate successful control of HIV infection 1 . Mutation within these epitopes can allow viral escape from CD8 + T-cell recognition. Here we analysed viral sequences and HLA alleles from >2,800 subjects, drawn from 9 distinct study cohorts spanning 5 continents. Initial analysis of the HLA-B*51-restricted epitope, TAFTIPSI (reverse transcriptase residues 128–135), showed a strong correlation between the frequency of the escape mutation I135X and HLA-B*51 prevalence in the 9 study cohorts ( P = 0.0001). Extending these analyses to incorporate other well-defined CD8 + T-cell epitopes, including those restricted by HLA-B*57 and HLA-B*27, showed that the frequency of these epitope variants ( n = 14) was consistently correlated with the prevalence of the restricting HLA allele in the different cohorts (together, P