NUCLEAR-LOCALIZATION OF THE TRUNCATED HEPATITIS-C VIRUS CORE PROTEIN WITH ITS HYDROPHOBIC C-TERMINUS DELETED

The core protein of hepatitis C virus (HCV) is considered to be cleave d from the N terminus of the large precursor polyprotein by cellular s ignalase. The HCV cDNA encoding the core protein was expressed (i) in monkey COS cells by a plasmid expression vector driven by the SR alpha promoter, and (ii) in insect cells by a recombinant baculovirus. The expressed product had an M(r) of 22 000 and was located in the cytopla sm. When the C-terminal hydrophobic domains were deleted, however, the truncated core proteins were translocated into the nucleus. The trunc ated core proteins were located in the nucleus even when they were exp ressed as a fusion protein with E. coli beta-galactosidase, which is e ssentially localized in the cytoplasm. Plasmids containing HCV cDNAs w ith a deletion in one of the regions encoding clusters of basic amino acids were expressed in COS cells and the localization of the core pro tein was examined. The residues PRRGPR were suggested to play an impor tant role in nuclear localization. HCV is an RNA virus and its life cy cle was originally considered to be confined to the cytoplasm; the pre sent study, however, suggests that the HCV core protein can translocat e into the nucleus under certain circumstances.