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Journal of Virology, January 2008, p. 859-870, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01816-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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{triangledown}

Juan P. Giraldo-Vela,1 Richard Rudersdorf,2 Chungwon Chung,2 Ying Qi,3 Lyle T. Wallace,2 Benjamin Bimber,2 Gretta J. Borchardt,2 Debra L. Fisk,2 Chrystal E. Glidden,2 John T. Loffredo,2 Shari M. Piaskowski,1 Jessica R. Furlott,2 Juan P. Morales-Martinez,2 Nancy A. Wilson,2 William M. Rehrauer,1 Jeffrey D. Lifson,4 Mary Carrington,3 and David I. Watkins1,2*

Department of Pathology and Laboratory Medicine,1 Wisconsin National Primate Research Center, University of Wisconsin—Madison, Madison, Wisconsin 53715,2 Laboratory of Genomic Diversity, SAIC—Frederick, Inc., National Cancer Institute, Frederick, Maryland 21702,3 AIDS Vaccine Program/Basic Research Program, SAIC—Frederick, Inc., National Cancer Institute, Frederick, Maryland 217024

Received 17 August 2007/ Accepted 24 October 2007

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.

* Corresponding author. Mailing address: Department of Pathology and Laboratory Medicine, University of Wisconsin—Madison, 555 Science Dr., Madison, WI 53711. Phone: (608) 265-3380. Fax: (608) 265-8084. E-mail: watkins{at}primate.wisc.edu

{triangledown} Published ahead of print on 7 November 2007.

Journal of Virology, January 2008, p. 859-870, Vol. 82, No. 2
0022-538X/08/$08.00+0     doi:10.1128/JVI.01816-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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