ECTOPIC EXPRESSION OF HEPATITIS-C VIRUS CORE PROTEIN DIFFERENTIALLY REGULATES NUCLEAR TRANSCRIPTION FACTORS

The putative core protein of hepatitis C virus (HCV) regulates cellula r growth and a number of cellular promoters. To further understand its effect, we investigated the role of the core protein in the endogenou s regulation of two distinct transcription factors, nuclear factor-kap pa B (NF-kappa B) and activating protein-1 (AP-1), and the related mit ogen-activated protein kinase kinase (MAPKK) and c-Jun N-terminal kina se (JNK). Stable cell transfectants expressing the HCV core protein su ppressed tumor necrosis factor (TNF)-induced NF-kappa B activation. Su pershift analysis revealed that NF-kappa B consists of p50 and p65 sub units. This correlated with inhibition of the degradation of I kappa B alpha, the inhibitory subunit of NF-kappa B. The effect was not speci fic to TNF, as suppression in core protein-expressing cells was also o bserved in response to a number of other inflammatory agents known to activate NF-kappa B. In contrast to the effect on NF-kappa B, the HCV core protein constitutively activated AP-1, which correlated with the activation of JNK and MAPKK, which are known to regulate AP-1. These o bservations indicated that the core protein targets transcription fact ors known to be involved in the regulation of inflammatory responses a nd the immune system.