EFFECTS OF TRANSFORMING GROWTH FACTOR-BETA-1 AGAINST THE INHIBITORY-ACTION OF INTERFERON ON DNA-SYNTHESIS AND VIRAL REPLICATION IN HEPATITIS-B VIRUS DNA-TRANSFECTED CELL

Studies were undertaken to examine the effects of recombinant human transforming growth factor beta 1 (TGF-beta-1) on DNA synthesis and antiviral actions of interferons (IFNs) in HepG2 cell, a hepatoma cell line, transfected with hepatitis B virus (HBV) DNA. The inhibitory effects of IFN-alpha and -gamma on DNA synthesis of HepG2 cells were enhanced in a dose-dependent manner by a simultaneous addition of TGF-beta. The degree of suppression by the reagents was greater in HBV-nontransfected cells than in transfected cells. Inhibition of DNA synthesis was not due to direct cytotoxic effects of the additives, since the viability of HepG2 cells was comparable in the control and treated cultures as determined by trypan blue exclusion. Treatment of HBV DNA-transfected HepG2 cells with IFNs resulted in decrease in production of HB surface and e antigens, and in the level of HBV DNA, but TGF-beta reversed the IFN-induced antiviral state in HBV DNA-transfected HepG2 cells. TGF-beta had no direct effect on HBV replication. These results indicate that rTGF-beta-1 exerts a differential effect against the inhibitory actions of IFN on DNA synthesis and viral replication in HepG2 cells.