HEPATITIS-B VIRUS TRANSACTIVATOR MHBS(T) - ACTIVATION OF NF-KAPPA-B, SELECTIVE-INHIBITION BY ANTIOXIDANTS AND INTEGRAL MEMBRANE LOCALIZATION

C-terminal truncation of the middle surface antigen from hepatitis B virus (MHBs) gives rise to a novel transactivating protein, called MHBs(t). In this study we show that MHBs(t) like the HBx protein of HBV, can cause nuclear appearance of NF-chi-B DNA binding activity and induce various chi-B-controlled reporter genes. While an inhibitor of protein kinase C could not block gene induction by MHBs(t), the antioxidants N-acetyl-L-cysteine (NAC) and pyrrolidine dithiocarbamate (PDTC) could potently suppress transactivation at mM and mu-M concentrations, respectively. Also, chi-B-dependent gene induction by the transactivator HBx was blocked. The effects were selective because PDTC did not interfere with MHBs(t) and HBx-induced activation of the c-fos promoter/enhancer, nor with the basal activity of several other reporter genes lacking functional NF-chi-B binding motifs. Our data suggest that induction of a prooxidant state is crucial for the activation of NF-chi-B by MHBs(t) and HBx and might be related to the hepatocarcinogenic potential of the viral proteins. MHBs(t) had a subcellular localization unusual for a viral transactivator: it appeared to be an integral membrane protein of the endoplasmic reticulum.