Dysregulation of both the cell cycle within the CD4(+) T cells and T cell responses is characteristic for pathogenic
HIV infection in humans and experimental SIV
infection in rhesus macaques. However, SIV
infection in sooty mangabeys does not lead to either an
AIDS-like disease or such CD4(+) T cell dysregulation. A previous study has highlighted a potential role for
cell cycle regulatory proteins in these distinct clinical outcomes. This study was performed to characterize the effect of SIV
infection on the expression of cell cycle-related molecules in CD4(+) T cells of rhesus macaques and sooty mangabeys in attempts to define activation-induced gene expression patterns associated with
disease resistance or susceptibility. First,
T cell receptor (TCR)-mediated cell activation induced gene expression profiles that were unique to CD4(+) T cells from SIV-naive sooty mangabeys and rhesus macaques. More importantly, distinct and reproducible gene expression patterns were detected in CD4(+) T cells as a result of in vivo SIV
infection in animals from each of the two species. In addition, SIV
infection in both species showed significant differential effects on TCR activation-induced expression with a reproducible alteration of 10 genes highlighted by discordant effects on expression of
Cyclin D3,
Cyclin B, and RAD17. Therefore SIV
infection in rhesus macaques and sooty mangabeys exhibits distinct and reproducible effects on cell cycle regulation in CD4(+) T cells during T cell activation that may be the basis for
disease susceptibility vs. resistance in these two species, respectively.