MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques

Shelby L. O'Connor, Jennifer J. Lhost, Ericka A. Becker, Ann M. Detmer, Randall C. Johnson, Caitlin E. MacNair, Roger W. Wiseman, Julie A. Karl, Justin M. Greene, Benjamin J. Burwitz, Benjamin N. Bimber, Simon M. Lank, Jennifer J. Tuscher, Edward T. Mee, Nicola J. Rose, Ronald C. Desrosiers, Austin L. Hughes, Thomas C. Friedrich, Mary Carrington, David H. O'Connor

Research output: Contribution to journalArticle

60 Scopus citations

Abstract

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 MHChomozygous 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 epitopespecific 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.

Original languageEnglish (US)
Pages (from-to)22ra18
JournalScience translational medicine
Volume2
Issue number22
DOIs
StatePublished - Jun 7 2010

    Fingerprint

ASJC Scopus subject areas

  • Medicine(all)

Cite this

O'Connor, S. L., Lhost, J. J., Becker, E. A., Detmer, A. M., Johnson, R. C., MacNair, C. E., Wiseman, R. W., Karl, J. A., Greene, J. M., Burwitz, B. J., Bimber, B. N., Lank, S. M., Tuscher, J. J., Mee, E. T., Rose, N. J., Desrosiers, R. C., Hughes, A. L., Friedrich, T. C., Carrington, M., & O'Connor, D. H. (2010). MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques. Science translational medicine, 2(22), 22ra18. https://doi.org/10.1126/scitranslmed.3000524