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

  1. Author:
    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.

  2. Author Address

    [O'Connor, Shelby L.; Lhost, Jennifer J.; Greene, Justin M.; Burwitz, Benjamin J.; O'Connor, David H.] Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA. [Becker, Ericka A.; Detmer, Ann M.; MacNair, Caitlin E.; Wiseman, Roger W.; Karl, Julie A.; Bimber, Benjamin N.; Lank, Simon M.; Tuscher, Jennifer J.; Friedrich, Thomas C.; O'Connor, David H.] Univ Wisconsin, Wisconsin Natl Primate Res Ctr, Madison, WI 53706 USA. [Johnson, Randall C.] NCI, Lab Genom Divers, Sci Applicat Int Corp, Frederick, MD 21702 USA. [Johnson, Randall C.] Conservatoire Natl Arts & Metiers, Chaire Bioinfromat, F-75003 Paris, France. [Mee, Edward T.; Rose, Nicola J.] Natl Inst Biol Stand & Controls, Div Retrovirol, Potters Bar EN6 3QG, Herts, England. [Desrosiers, Ronald C.] Harvard Univ, New England Primate Res Ctr, Sch Med, Southborough, MA 01772 USA. [Hughes, Austin L.] Univ S Carolina, Dept Biol Sci, Columbia, SC 29208 USA. [Carrington, Mary] NCI, Canc & Inflammat Program, Sci Applicat Int Corp, Frederick, MD 21702 USA. [Carrington, Mary] Ragon Inst MGH MIT & Harvard, Boston, MA 02114 USA.;O'Connor, DH, Univ Wisconsin, Dept Pathol & Lab Med, Madison, WI 53706 USA.;doconnor@primate.wisc.edu
    1. Year: 2010
    2. Date: Mar
  2. Journal: Science Translational Medicine
    1. 2
    2. 22
    3. Pages: 9
  4. Type of Article: Article
  5. Article Number: 22ra18
  6. ISSN: 1946-6234
  1. 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 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.

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External Sources

  1. View Full Text
  2. DOI: 10.1126/scitranslmed.3000524
  3. View record in Web of Science®
  4. WOS: 000277303900002

Library Notes

  1. Fiscal Year: FY2009-2010
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