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Journal of Virology, March 2008, p. 3139-3146, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.02102-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Selective Downregulation of Rhesus Macaque and Sooty Mangabey Major Histocompatibility Complex Class I Molecules by Nef Alleles of Simian Immunodeficiency Virus and Human Immunodeficiency Virus Type 2{triangledown}

M. Quinn DeGottardi,1 Anke Specht,2 Benjamin Metcalf,3 Amitinder Kaur,3 Frank Kirchhoff,2 and David T. Evans1*

Department of Microbiology and Molecular Genetics,1 Division of Immunology, New England Primate Research Center, Harvard Medical School, Southborough, Massachusetts 01772,3 Institute of Virology, Universitaetsklinikum, 89081 Ulm, Germany2

Received 21 September 2007/ Accepted 3 January 2008

Human immunodeficiency virus type 1 (HIV-1) Nef downregulates HLA-A and -B molecules, but not HLA-C or -E molecules, based on amino acid differences in their cytoplasmic domains to simultaneously evade cytotoxic T lymphocyte (CTL) and natural killer cell surveillance. Rhesus macaques and sooty mangabeys express orthologues of HLA-A, -B, and -E, but not HLA-C, and many of these molecules have unique amino acid differences in their cytoplasmic tails. We found that these differences also resulted in differential downregulation by primary simian immunodeficiency virus (SIV) SIVsmm/mac and HIV-2 Nef alleles. Thus, selective major histocompatibility complex class I downregulation is a conserved mechanism of immune evasion for pathogenic SIV infection of rhesus macaques and nonpathogenic SIV infection of sooty mangabeys.

* Corresponding author. Mailing address: Department of Microbiology and Molecular Genetics, New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, MA 01772-9102. Phone: (508) 624-8025. Fax: (508) 786-3317. E-mail: devans{at}hms.harvard.edu

{triangledown} Published ahead of print on 16 January 2008.

Journal of Virology, March 2008, p. 3139-3146, Vol. 82, No. 6
0022-538X/08/$08.00+0     doi:10.1128/JVI.02102-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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