The November issue of the Journal of Clinical Investigation (JCI) contains an excellent review of research investigating the benign nature of SIV infection in natural hosts (sooty mangabeys and African green monkeys). Guido Silvestri and colleagues outline current knowledge about the differences between non-pathogenic and pathogenic immunodeficiency virus infections with an emphasis on the now well-accepted role of immune activation in determining disease outcome.
The authors also offer the intriguing suggestion that perhaps non-pathogenic SIV infections have less impact on the function of CD4 T cells because the CD4 T cells that are infected are at a later stage of differentiation and are destined to undergo activation-induced death anyway; in this model, important self-renewing central memory CD4 T cells are not as disrupted by SIV and thus immunodeficiency does not ensue (see image). While speculative, this represents an interesting area for future research.
The authors conclude by stressing that studies of benign SIV infections have made a huge contribution to understanding the pathogenesis of HIV infection in humans, and emphasize that additional studies will likely provide additional important insights, as well as potentially revealing new therapeutic targets for the treatment of the HIV and AIDS. As with all JCI content, access to the full text of the paper is free of charge.
J. Clin. Invest. 117:3148-3154 (2007). doi:10.1172/JCI33034.
Science in Medicine
Understanding the benign nature of SIV infection in natural hosts
Guido Silvestri1,2, Mirko Paiardini1, Ivona Pandrea3,4, Michael M. Lederman4 and Donald L. Sodora5
1Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
2Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
3Tulane National Primate Research Center, Tulane Health Sciences Center, Tulane University, Covington, Louisiana, USA.
4Department of Medicine, Case Western Reserve University, Cleveland, Ohio, USA.
5Department of Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
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.
I haven’t read the review, but I have heard a number of different hypotheses for the differences in pathogenesis. The one thing they have in common is that SIV does not cause chronic immune activation. Frank Kirchoff has data showing that SIV nef downregulates CD3, while HIV nef does not. Louis Picker claims that it is a difference in T cell homeostasis, with certain CD4 subsets being depleted. Similarly, Aftab Ansari’s data show differences in T cell activation. I am sure there are many, many other studies out there of which I am unaware. A good review would be helpful in clarifying where all of this research intersects.
Posted by: Michael Linde | November 21, 2007 at 11:32 AM