1. ¹Unité de Physiopathologie des Infections Lentivirales, Institut Pasteur, Paris, cedex 15, France
2. ²Unité de Biologie des Rétrovirus, Institut Pasteur, Paris, France
3. ³Emory Vaccine Center, 954 Gatewood Rd NE, Atlanta, GA, USA
4. ⁴This work is dedicated to the memory of Bruno Hurtrel

Correspondence: J Estaquier, Unite de physiopathologie des infections lentivirales, Institut Pasteur, 28 rue du Dr roux, Paris, France. Tel: +33 1 45 68 89 15; Fax: +33 1 40 61 34 50; E-mail: jestaqui@pasteur.fr

Received 24 November 2004; Revised 3 January 2005; Accepted 4 January 2005; Published online 1 April 2005.

Abstract

Pathogenic human immunodeficiency virus (HIV)/Simian immunodeficiency virus (SIV) infection is associated with increased T-cell apoptosis. In marked contrast to HIV infection in humans and SIV infection in macaques, the SIV infection of natural host species is typically nonpathogenic despite high levels of viral replication. In these nonpathogenic primate models, no observation of T-cell apoptosis was observed, suggesting that either SIV is less capable of directly inducing apoptosis in natural hosts (likely as a result of coevolution/coadaptation with the host) or, alternatively, that the indirect T-cell apoptosis plays the key role in determining the HIV-associated T-cell depletion and progression to acquired immune deficiency syndrome (AIDS). Understanding the molecular and cellular mechanisms responsible for the disease-free equilibrium in natural hosts for SIV infection, including those determining the absence of high levels of T-cell apoptosis, is likely to provide important clues regarding the mechanisms of AIDS pathogenesis in humans.