Suppression of TGF-β signaling in vitro by HTLV-I Tax and in HTLV-I–infected patients. (A) Schematic diagram of the TGF-β signaling pathway. HepG2 cells were transfected with either a (B) synthetic TGF-β/Smad reporter vector (3TP-luc), (C) Smad7 promoter construct, or (H) TGF-βRII promoter construct in combination with the indicated expression vectors and/or rhTGF-β1. Error bars represent SEM. After 24 hours, cell lysates were assayed for luciferase activity. Total RNA from CD4⁺ T cells from 10 healthy donors (HD), 3 HTLV-I–infected asymptomatic carriers (AC), and 10 patients with HAM/TSP were assayed for endogenous (D) Smad7, (E) Smad3, (F) Smad4, or (G) TGF-βRII mRNA expression by real-time RT-PCR (TaqMan). The horizontal bar represents the median. (I) A statistically significant negative correlation (P = .022, R² = 0.50) between the HTLV-I tax proviral load in PBMCs and the TGF-βRII mRNA expression in CD4⁺ T cells was observed in HTLV-I–infected patients.