Since SMAD protein regulates the fate of SMAD-dependent TGF-β-induced biological activities, and since several studies have described SMAD signaling deregulation in association with various pathological conditions like tumor progression [21], neurological disorders [22], tissue fibrosis [19], aberrant immune response [23], and inflammation [24], we hypothesized that interference with the SMAD signaling pathway might also play an important part in TGF-β-induced HIV/SIV pathogenesis. This evidence concerns the gene TGFB1 and nervous system disorder.