|Budget Amount *help
¥3,600,000 (Direct Cost : ¥3,600,000)
Fiscal Year 2002 : ¥1,300,000 (Direct Cost : ¥1,300,000)
Fiscal Year 2001 : ¥2,300,000 (Direct Cost : ¥2,300,000)
Chronic infection of hepatitis C virus (HCV) is considered to cause the development of chronic hepatitis, liver cirrohsis, and hepatocellular carcinoma. We tried, therefore, to reveal the molecular mechanism of NF-κB activation by the HCV core protein (the core) which has been suggested to be related with the persistent infection of this virus. Using the yeast two hybrid screening system, we obtained several candidates of cellular factors interacting with the core. One of the candidates was Sp110b, which was reported to be a splicing variant of Sp110, a transcriptional cofactor of retinoic acid receptor (RAR). As we observed that the core enhanced the transcriptional activity of RAR, finer analyses for the relationship between the core and Sp110b were performed. Expression level of Sp110b mRNA was higher than that of Sp110. We also observed that overproduction of Sp110b suppressed the RAR-dependent transcriptional activation, suggesting that Sp110b is a negative cofactor of RAR-dependent transcription. We found that the subcellular localization of Sp110b which was originally located in the nucleus was changed to the perinuclear cytoplasmic region, when the core was coproduced in the cells. That change as well as the enhancement of RAR-dependent transcriptional activation was reverted by the coproduction of minimum region of Sp110b required for binding with the core, suggesting that the interaction between the core and Sp110b is important for those phenomenons. As a transcriptional cofactor has been revealed to be related with several transcriptional events, we now examine the contribution of Sp110b to the activation of NF-κB by the core.
Furthermore, we have established the cell line in which HCV genomic replicon including whole HCV genome was replicated and maintained in order to examine the effect of the core in such cells. The analysis of function of Sp110b on the HCV genome replication is underway by using this cell line.