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Humans with chimpanzee-like major histocompatibility complex-specificities control HIV-1 infection

Hoof, Ilkaa; Keşmir, Cana,b; Lund, Olea; Nielsen, Mortena

doi: 10.1097/QAD.0b013e328302f39f
Basic Science: Concise Communications

Background: Major histocompatibility complex (MHC) class I molecules allow immune surveillance by presenting a snapshot of the intracellular state of a cell to circulating cytotoxic T lymphocytes. The MHC class I alleles of an HIV-1 infected individual strongly influence the level of viremia and the progression rate to AIDS. Chimpanzees control HIV-1 viral replication and develop a chronic infection without progressing to AIDS. A similar course of disease is observed in human long-term non-progressors.

Objective: To investigate if long-term non-progressors and chimpanzees have functional similarities in their MHC class I repertoire.

Methods: We compared the specificity of groups of human MHC molecules associated with different levels of viremia in HIV-1 infected individuals with those of chimpanzee.

Results and conclusion: We demonstrate that human MHC with control of HIV-1 viral load share binding motifs with chimpanzee MHC. Moreover, we find that chimpanzee and human MHC associated with low viral load are predicted to elicit broader Gag-specific immune responses than human MHC associated with high viral load, thus supporting earlier findings that Gag-specific immune responses are essential for HIV-1 control.

From the aCenter for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Lyngby, Denmark

bDepartment of Theoretical Biology/Bioinformatics and the Academic Biomedical Centre, Utrecht University, The Netherlands.

Received 31 January, 2008

Revised 26 March, 2008

Accepted 1 April, 2008

Correspondence to Ilka Hoof, Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Kemitorvet, Building 208, Lyngby 2800, Denmark. Tel: +45 45 25 61 27; fax: +45 45 93 15 85; e-mail: ilka@cbs.dtu.dk

© 2008 Lippincott Williams & Wilkins, Inc.