MHC Heterozygote Advantage in Simian Immunodeficiency Virus–Infected Mauritian Cynomolgus Macaques

• Published in: Science translational medicine 2010-03, Vol.2 (22), p.22ra18-22ra18
• Main Authors: O'Connor, Shelby L, Lhost, Jennifer J, Becker, Ericka A, Detmer, Ann M, Johnson, Randall C, Macnair, Caitlin E, Wiseman, Roger W, Karl, Julie A, Greene, Justin M, Burwitz, Benjamin J, Bimber, Benjamin N, Lank, Simon M, Tuscher, Jennifer J, Mee, Edward T, Rose, Nicola J, Desrosiers, Ronald C, Hughes, Austin L, Friedrich, Thomas C, Carrington, Mary, O'Connor, David H
• Format: Article
• Language: English
• Subjects: Animals; Base Sequence; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - virology; Chronic Disease; Haplotypes - genetics; Heterozygote; Homozygote; Macaca fascicularis - genetics; Macaca fascicularis - immunology; Macaca fascicularis - virology; Major Histocompatibility Complex - immunology; Mauritius; Molecular Sequence Data; Simian Acquired Immunodeficiency Syndrome - complications; Simian Acquired Immunodeficiency Syndrome - genetics; Simian Acquired Immunodeficiency Syndrome - immunology; Simian Acquired Immunodeficiency Syndrome - virology; Simian Immunodeficiency Virus - genetics; Simian Immunodeficiency Virus - immunology; Simian Immunodeficiency Virus - isolation & purification; Simian Immunodeficiency Virus - physiology; Viremia - complications; Viremia - genetics; Viremia - immunology; Viremia - virology
• ISSN: 1946-6234; 1946-6242; 1946-6242
• DOI: 10.1126/scitranslmed.3000524

The importance of a broad CD8 T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. We examined viral loads in simian immunodeficiency virus (SIV)–infected major histocompatibility complex (MHC)–homozygous and MHC-heterozygous Mauritian cynomolgus macaques. Chronic viremia in MHC-homozygous macaques was 80 times that in MHC-heterozygous macaques. Virus from MHC-homozygous macaques accumulated 11 to 14 variants, consistent with escape from CD8-TL responses after 1 year of SIV infection. The pattern of mutations detected in MHC-heterozygous macaques suggests that their epitope-specific CD8-TL responses are a composite of those present in their MHC-homozygous counterparts. These results provide the clearest example of MHC heterozygote advantage among individuals infected with the same immunodeficiency virus strain, suggesting that broad recognition of multiple CD8-TL epitopes should be a key feature of HIV vaccines.