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Purpose of Review: 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., Recent Findings: 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., Summary: 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.

Background: The three divergent HIV-1 groups M, N and O were very probably introduced into the human population by independent cross-species transmissions of SIVcpz from the chimpanzee subspecies Pan troglodytes troglodytes in central Africa., Objective: To characterize HIV-1 group N strains and to elucidate the group's epidemiology and relationship to HIV-1 strains O and M, and SIVcpz., Methods: DNA amplification, sequencing and phylogenetic analyses were performed to characterize viruses from three group N-infected individuals (YBF106, YBF115 and YBF116) together with YBF30 and YBF105 previously described., Results: Full-length genome sequence was determined for virus YBF106; gag, pol and env sequences were obtained for YBF116; pol (integrase) and env (gp41) fragments were obtained for YBF115. The gag, pol, 5'-vif and nef sequences were phylogenetically more closely related to HIV-1 M while 3'-vif, vpr, tat, vpu and env clustered with SIVcpz from P. t. troglodytes. Sequence analysis revealed no mutations potentially responsible for drug resistance., Conclusions: The finding that all group N viruses displayed the same recombinant structure and were monophyletic indicates that a single transfer event of SIVcpz to humans can account for the origin of this group. Despite the pathogenic outcome of the known group N infections, the extremely low prevalence of this divergent HIV-1 suggests that this group is not an emerging threat to human health at the present time. However, continuous monitoring of HIV-1 diversity will be important to survey the potential of unusual HIV infections, such as group N, to contribute to the HIV/AIDS pandemic.