Cariporide, a selective Na+/H+ exchange inhibitor, decreases liver fibrosis in the bile duct ligated rat

Results: We demonstrate 1) That both core tumour and non-tumourderived sequences inhibit the global antiviral effects of IFNa on VSV and EMCV replication in Ratl and HuH7 cells and sensitize Ref cells to transformation, in cooperation with ras oncogene. 2) That tumour and nontumour derived cores show, however, a quite distinct pattern of biological effects on IFNa signaling: inhibition of global antiviral effect of IFNa in tumour-derived expressing cells is much less pronounced, compared with non tumour-derived and reference lb cores.Expression of tumour-derived, and not non-tumour-derived nor reference lb cores, induces transactivafion of 0interferon sensitive response element0 (ISRE); tumour-derived core also increases phosphorylation of Statl and Stat 2, compared with nontumour-derived and reference lb proteins.Tumour-derived core show a markedly increased transforming activity in REF cells, in cooperation with ras oncogene, compared with non-tumour-derived and reference lb cores. Conclusion: Our data 1) support a role for HCV core in the resistance to global antiviral effect of IFNa (despite ISRE activation) and cell transformation in REF cells. 2) demonstrate a distinct pattern of biological effects of tumour and non-tumour-derived cores on interferon signaling and cell transformation, correlated with the hypothesis of selection of core mutants in clonaly expanding liver cells. Data obtained with 3 additional tumour and non-tumour-derived core sequences will be discussed.