SMAD7 and infection: However, the sustained production of TGF-β1 throughout the acute/subacute phases of SIVmac infection of rhesus macaques was found to be associated with upregulation of Smad7, an inhibitor of TGF-β signaling, raising the hypothesis that early protective effects of TGF-β1 may become blunted by subacute infection due to leukocytes becoming less responsive to this cytokine (59).