WILD-TYPE, BUT NOT MUTANT-TYPE, P53 ENHANCES NUCLEAR ACCUMULATION OF THE NS3 PROTEIN OF HEPATITIS-C VIRUS

By using vaccinia virus-T7 hybrid expression system, subcellular local ization of the NS3 protein of hepatitis C virus was studied. Full-size NS3 (NS3F) and a carboxy-terminally truncated form (NS3 Delta C) were localized in the cytoplasm and the nucleus when expressed alone. Howe ver, NS3F and NS3 Delta C, but not amino- and carboxy-terminally trunc ated form (NS3 Delta N Delta C), were each co-localized with wild-type p53 almost exclusively in the nucleus upon co-expression. The wild-ty pe p53-induced nuclear accumulation of NS3F was inhibited only partial ly by NS4A. When co-expressed with mutant-type p53, NS3F and NS3 Delta C were each co-localized with it exclusively in the cytoplasm. Taken together, the present results suggest that wild-type p53 enhances nucl ear accumulation of NS3F and NS3 Delta C through the involvement of th eir amino-terminal sequences even in the presence of NS4A, and that mu tant-type p53 inhibits their nuclear, and enhances their cytoplasmic, accumulation. (C) 1997 Academic Press