A key factor driving AIDS-associated immunopathogenesis is chronic immune activation. Simian immunodeficiency virus (SIV) infection of African natural host species leads to high viremia, but low immune activation and absence of disease. Considerable progress in our understanding of pathological immune activation has come from comparative studies of SIV infection in pathogenic Asian macaque species and natural hosts. The focus of this review is to highlight recent work on the natural host model using high-throughput genomics.
Several groups have independently conducted microarray gene expression profiling comparing in-vivo SIV infection in natural and non-natural hosts. A consistent finding between these studies is that both pathogenic SIV infection of macaques and nonpathogenic infections of natural hosts have strong induction of interferon-stimulated genes (ISGs) early on, but a key difference was that natural hosts down-modulated the interferon response rapidly after acute infection. The development of new genome-based resources for further study of the natural host model is discussed.
Initial efforts using high-throughput biology to study SIV infection of natural hosts have effectively identified the ability of natural hosts to resolve interferon responses and immune activation. Further application of ‘omic-based technologies coupled with integrative systems-based analysis should continue to yield progress.
aYerkes National Primate Research Center, and Emory Vaccine Center, Emory University, Atlanta, Georgia, USA
bInstitut Pasteur, Unité Régulation des Infections Rétrovirales, Paris
cInstitut des Hautes Études Scientifiques, Bures sur Yvette
dVaccine Research Institute, INSERM U955, Institut Mondor de Recherche Biomédicale, Créteil, France
Correspondence to Michaela Müller-Trutwin, Unité de Régulation des Infections Rétrovirales, Institut Pasteur, 25 rue du Dr Roux, 75015 Paris, France.Tel: +33 1 40613969; fax: +33 1 45688957; e-mail: firstname.lastname@example.org