The Core Protein of Hepatitis C Virus Is Imported into the Nucleus by Transport Receptor Kap123p but Inhibits Kap121p-dependent Nuclear Import of Yeast AP1-like Transcription Factor in Yeast Cells

The core protein of hepatitis C virus (HCV) is a major component of the viral nucleocapsid. The HCV core protein includes nuclear localization signal-like sequences and has various effects on cellular metabolism, playing roles, for example, in the regulation of transcription, apoptosis, and transformation. To examine the possibility of an effect of the core protein on nucleocytoplasmic transport, we used the yeast Saccharomyces cerevisiae as a model system. The core protein (p23) is processed to p21 and is localized in both the cytoplasm and nucleus in yeast cells, similar to that observed in mammalian cells in several cases. The nuclear import of the core protein requires the activity of small GTPase Ran/Gsp1p and is mediated by Kap123p in yeast cells. When the core protein was expressed in yeast cells, the import of the yeast AP1-like transcription factor Yap1p into the nucleus was inhibited. Experiments in vitro involving Kap121p, also known as Pse1p, a receptor for the nuclear import of Yap1p, indicated that the amount of Yap1p bound to Kap121p was reduced in the presence of core protein. These results suggest that the HCV core protein affects cellular metabolism by disturbing transport of proteins to the nucleus.