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 localization of the NS3 protein of hepatitis C virus was studied. Full-size NS3 (NS3F) and a carboxy-terminally truncated form (NS3ΔC) were localized in the cytoplasm and the nucleus when expressed alone. However, NS3F and NS3ΔC, but not amino- and carboxy-terminally truncated form (NS3ΔNΔC), were each co-localized with wild-type p53 almost exclusively in the nucleus upon co-expression. The wild-type p53-induced nuclear accumulation of NS3F was inhibited only partially by NS4A. When co-expressed with mutant-type p53, NS3F and NS3ΔC were each co-localized with it exclusively in the cytoplasm. Taken together, the present results suggest that wild-type p53 enhances nuclear accumulation of NS3F and NS3ΔC through the involvement of their amino-terminal sequences even in the presence of NS4A, and that mutant-type p53 inhibits their nuclear, and enhances their cytoplasmic, accumulation.