Adaptation of HIV-1 to human leukocyte antigen class I.


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. 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 < 0.0001), demonstrating strong evidence of HIV adaptation to HLA at a population level. This process of viral adaptation may dismantle the well-established HLA associations with control of HIV infection that are linked to the availability of key epitopes, and highlights the challenge for a vaccine to keep pace with the changing immunological landscape presented by HIV.

DOI: 10.1038/nature07746

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@article{Kawashima2009AdaptationOH, title={Adaptation of HIV-1 to human leukocyte antigen class I.}, author={Yuka Kawashima and Katja J. Pfafferott and John A. Frater and Philippa C Matthews and Rebecca P Payne and Marylyn Martina Addo and Hiroyuki Gatanaga and Mamoru Fujiwara and Atsuko Hachiya and Hirokazu Koizumi and Nozomi Kuse and Shinichi Oka and Anna Krystyna Duda and Andrew J. Prendergast and Hayley Crawford and Alasdair J. Leslie and Zabrina L. Brumme and Chanson J. Brumme and Todd M. Allen and Christian Brander and Richard A. Kaslow and James Jianming Tang and Eric Hunter and Susan Allen and Joseph Mulenga and Songee L Branch and Tim Roach and M Anne St John and Simon A Mallal and Anthony C Ogwu and Roger L. Shapiro and Julia G. Prado and Sarah J. Fidler and Jonathan Weber and Oliver G. Pybus and Paul Klenerman and Thumbi Ndung'u and Rodney E. Phillips and David Heckerman and P. Richard Harrigan and Bruce D. Walker and Masafumi Takiguchi and Philip J. R. Goulder}, journal={Nature}, year={2009}, volume={458 7238}, pages={641-5} }