The generalized T-cell activation characterizing HIV-1 and SIVmac infections in humans and macaques (MACs) is not found in the non-pathogenic SIVagm infection in African green monkeys (AGMs). We have previously shown that TGF-β1, Foxp3 and IL-10 are induced very early after SIVagm infection. In SIVmac-infected MACs, plasma TGF-β1 induction persists during primary infection [1]. We raised the hypothesis that MACs are unable to respond to TGF-β1 and thus cannot resorb virus-driven inflammation. We therefore compared the very early expression dynamics of pro- and anti-inflammatory markers as well as of factors involved in the TGF-β1 signaling pathway in SIV-infected AGMs and MACs.

Levels of transcripts encoding for pro- and anti-inflammatory markers (tnf-α, ifn-γ, il-10, t-bet, gata-3) as well as for TGF-β1 signaling mediators (smad3, smad4, smad7) were followed by real time PCR in a prospective study enrolling 6 AGMs and 6 MACs.

During primary SIVmac infection, up-regulations of tnf-α, ifn-γ and t-bet responses (days 1–16 p.i.) were stronger whereas il-10 response was delayed (4^th week p.i.) compared to SIVagm infection. Up-regulation of smad7 (days 3–8 p.i.), a cellular mediator inhibiting the TGF-β1 signaling cascade, characterized SIV-infected MACs. In AGMs, we found increases of gata-3 but not t-bet, a longer lasting up-regulation of smad4 (days 1–21 p.i), a mediator enhancing TGF-β1 signaling, and no smad7 up-regulations.

Our data suggest that the inability to resorb virus-driven inflammation and activation during the pathogenic HIV-1/SIVmac infections is associated with an unresponsiveness to TGF-β1.