Understanding the benign nature of SIV infection in natural hosts

Abstract

In striking contrast to HIV infection, natural SIV infection of African nonhuman primates is asymptomatic and usually does not induce significant CD4 + T cell depletion despite high levels of virus replication. Recently, significant progress has been made in understanding the mechanisms underlying the remarkable difference in infection outcome between natural and nonnatural HIV/ SIV hosts. These advances include the identification of limited immune activation as a key factor protecting natural SIV hosts from AIDS and the discovery of low CC chemokine receptor 5 expression on CD4 + T cells as a specific and consistent immunologic feature in these animals. Further elucidation of the pathways by which the differences in immune activation between natural and nonnatural hosts are manifest holds promise for the design of novel therapeutic approaches to HIV infection.Nonstandard abbreviations used: AGM, African green monkey; CCR5, CC chemokine receptor 5; CXCR4, CXC chemokine receptor 4; LTNP, long-term nonprogressor; MALT, mucosa-associated lymphoid tissue; NHP, nonhuman primate; RM, rhesus macaque; SM, sooty mangabey.

Immune Activation Driven by CTLA-4 Blockade Augments Viral Replication at Mucosal Sites in Simian Immunodeficiency Virus Infection

“…The study presented here therefore complements work of others demonstrating that the low level of immune activation in Sooty may be related to the lack of progression to AIDS, despite the high levels of SIV replication (13).…”

“…Thus, in the pathogenic SIV model, the relative contribution of direct CD4 ϩ T cell killing and/or immune activation in disease progression, particularly at mucosal sites, remains unclear. In contrast, natural SIV infection of African nonhuman primates is asymptomatic and the lack of disease progression in this model has been linked to a low level of immune activation (13).…”

The Quality of Chimpanzee T-Cell Activation and Simian Immunodeficiency Virus/Human Immunodeficiency Virus Susceptibility Achieved via Antibody-Mediated T-Cell Receptor/CD3 Stimulation Is a Function of the Anti-CD3 Antibody Isotype

“…It is thought that a better understanding of this phenomenon could result in the development of novel immune-based therapies for human immunodeficiency virus type 1 (HIV-1) infection. For example, SIV infection in sooty mangabeys (Cercocebus atys) has a benign clinical course compared to the pathology of HIV-1 infection (23). Possible explanations for this finding have been intensely investigated.…”

Functions of the Lentiviral Accessory Protein Nef During the Distinct Steps of HIV and SIV Replication Cycle

“…HIV-1 Nef has also been reported to directly enhance the responsiveness of T cells to activation (Fenard et al, 2005;Fortin et al, 2004;. Nonetheless, non-human primates naturally infected with their species-specific SIVs (e.g., sooty mangabeys (SMs) and African green monkeys (AGMs)) generally do not show signs of progression to SAIDS (Silvestri et al, 2007;VandeWoude and Apetrei, 2006). The mechanism underlying the remarkable difference in the outcome of infection between these primate hosts include T cell activation as a strong predictor of progression to AIDS (Giorgi et al, 1999;Sousa et al, 2002).…”