The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers

Juan P. Giraldo-Vela, Richard Rudersdorf, Won Chung, Ying Qi, Lyle T. Wallace, Benjamin Bimber, Gretta J. Borchardt, Debra L. Fisk, Chrystal E. Glidden, John T. Loffredo, Shari M. Piaskowski, Jessica R. Furlott, Juan P. Morales-Martinez, Nancy A. Wilson, William M. Rehrauer, Jeffrey D. Lifson, Mary Carrington, David I. Watkins

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

The role of CD4+ T cells in the control of human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) replication is not well understood. Even though strong HIV- and SIV-specific CD4 + T-cell responses have been detected in individuals that control viral replication, major histocompatibility complex class II (MHC-II) molecules have not been definitively linked with slow disease progression. In a cohort of 196 SIVmac239-infected Indian rhesus macaques, a group of macaques controlled viral replication to less than 1,000 viral RNA copies/ml. These elite controllers (ECs) mounted a broad SIV-specific CD4+ T-cell response. Here, we describe five macaque MHC-II alleles (Mamu-DRB*w606, -DRB*w2104, -DRB1*0306, -DRB1*1003, and -DPB1*06) that restricted six SIV-specific CD4+ T-cell epitopes in ECs and report the first association between specific MHC-II alleles and elite control. Interestingly, the macaque MHC-II alleles, Mamu-DRB1*1003 and -DRB1*0306, were enriched in this EC group (P values of 0.02 and 0.05, respectively). Additionally, Mamu-B*17-positive SIV-infected rhesus macaques that also expressed these two MHC-II alleles had significantly lower viral loads than Mamu-B*17-positive animals that did not express Mamu-DRB1*1003 and -DRB1*0306 (P value of <0.0001). The study of MHC-II alleles in macaques that control viral replication could improve our understanding of the role of CD4+ T cells in suppressing HIV/SIV replication and further our understanding of HIV vaccine design.

Original languageEnglish (US)
Pages (from-to)859-870
Number of pages12
JournalJournal of virology
Volume82
Issue number2
DOIs
StatePublished - Jan 1 2008
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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    Giraldo-Vela, J. P., Rudersdorf, R., Chung, W., Qi, Y., Wallace, L. T., Bimber, B., Borchardt, G. J., Fisk, D. L., Glidden, C. E., Loffredo, J. T., Piaskowski, S. M., Furlott, J. R., Morales-Martinez, J. P., Wilson, N. A., Rehrauer, W. M., Lifson, J. D., Carrington, M., & Watkins, D. I. (2008). The major histocompatibility complex class II alleles Mamu-DRB1*1003 and -DRB1*0306 are enriched in a cohort of simian immunodeficiency virus-infected rhesus macaque elite controllers. Journal of virology, 82(2), 859-870. https://doi.org/10.1128/JVI.01816-07