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 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

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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)
JournalScience Translational Medicine
Volume2
Issue number22
DOIs
StatePublished - 2010
Externally publishedYes

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Simian Immunodeficiency Virus
Macaca
Heterozygote
Major Histocompatibility Complex
T-Lymphocytes
Viruses
AIDS Vaccines
T-Lymphocyte Epitopes
Viremia
Virus Diseases
Viral Load
Epitopes
HIV
Mutation

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., ... O'Connor, D. H. (2010). MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques. Science Translational Medicine, 2(22). https://doi.org/10.1126/scitranslmed.3000524

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

In: Science Translational Medicine, Vol. 2, No. 22, 2010.

Research output: Contribution to journalArticle

O'Connor, SL, Lhost, JJ, Becker, EA, Detmer, AM, Johnson, RC, MacNair, CE, Wiseman, RW, Karl, JA, Greene, JM, Burwitz, B, Bimber, BN, Lank, SM, Tuscher, JJ, Mee, ET, Rose, NJ, Desrosiers, RC, Hughes, AL, Friedrich, TC, Carrington, M & O'Connor, DH 2010, 'MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques', Science Translational Medicine, vol. 2, no. 22. https://doi.org/10.1126/scitranslmed.3000524
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 ; 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. / MHC heterozygote advantage in simian immunodeficiency virus-infected Mauritian cynomolgus macaques. In: Science Translational Medicine. 2010 ; Vol. 2, No. 22.
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