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Journal of Virology, July 2007, p. 7584-7597, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.02616-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Human and Simian Immunodeficiency Virus-Mediated Upregulation of the Apoptotic Factor TRAIL Occurs in Antigen-Presenting Cells from AIDS-Susceptible but Not from AIDS-Resistant Species ^,

Nayoung Kim,¹ Alicja Dabrowska,¹ Richard G. Jenner,² and Anna Aldovini^1*

Children's Hospital Boston, Department of Medicine, and Harvard Medical School, Department of Pediatrics, Boston, Massachusetts 02115,¹ Whitehead Institute for Biomedical Research, 9 Cambridge Center, Cambridge, Massachusetts 02142²

Received 27 November 2006/ Accepted 16 April 2007

Human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) infections lead to AIDS in humans and rhesus macaques (RM), while they are asymptomatic in species naturally infected with SIV, such as chimpanzees, sooty mangabeys (SM), and African green monkeys (AGM). Differential CD4⁺ T-cell apoptosis may be responsible for these species-specific differences in susceptibility to disease. To identify factors that influence the different apoptotic responses of these species, we analyzed virus-infected human and nonhuman primate peripheral blood mononuclear cells (PBMC). We found that the apoptotic factor TRAIL was present at higher levels in human and RM PBMC cultures and was mediating, at least in part, CD4⁺ T-cell apoptosis in these cultures. The species-specific increase in TRAIL and death receptor expression observed with cultures also occurred in vivo in SIV-infected RM but not in SIV-infected SM. In human and RM myeloid immature dendritic cells and macrophages, the virus-induced expression of TRAIL and other interferon-inducible genes, which did not occur in the same cells from chimpanzee, SM, and AGM, was Tat dependent. Our results link the differential induction of TRAIL in human and nonhuman primate cells to species-specific differences in disease susceptibility.

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* Corresponding author. Mailing address: Children's Hospital Boston, 300 Longwood Avenue, Boston, MA 02115. Phone: (617) 919-2891. Fax: (617) 730-0255. E-mail: anna.aldovini{at}childrens.harvard.edu

Published ahead of print on 9 May 2007.

Supplemental material for this article may be found at http://jvi.asm.org/.

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Journal of Virology, July 2007, p. 7584-7597, Vol. 81, No. 14
0022-538X/07/$08.00+0     doi:10.1128/JVI.02616-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

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