REGULATED PROCESSING OF HEPATITIS-C VIRUS CORE PROTEIN IS LINKED TO SUBCELLULAR-LOCALIZATION

Posttranslational processing and subcellular localization of the HCV c ore protein are critical steps involved in the assembly of hepatitis C virus (HCV). In this study, both of these events were investigated by in vitro translation and transient COS-1 cell transfection of core pr otein expression constructs. Mutations at amino acid residues 173 to 1 74 and 191 to 192 disrupted processing events at the two putative clea vage sites in the C-terminal hydrophobic region of the core protein, i ndicating that these residues are implicated in the pathway of core pr otein maturation. As a result, two forms of core protein, C173 and C19 1, were detected by immunoblotting. Indirect immunofluorescence experi ments showed that core proteins C173 and C191, when produced from HCV fall-length protein or various polyprotein precursors, displayed a cyt oplasmic localization. The C173 species, however, was translocated to the nucleus when expressed in the absence of C191. These findings indi cate that preferential cleavage may occur during core protein maturati on and that the association of the C191 with the C173 species may cont ribute to the distinct subcellular distribution of core protein. This may provide a possible mechanism for the control of the diverse biolog ical functions of core protein during HCV replication and assembly.