The HCV core protein acts as a positive regulator of Fas-mediated apoptosis in a human lymphoblastoid T cell line

Hepatitis C virus (HCV) is a major human pathogen causing mild to severe li ver disease worldwide and is remarkably efficient at establishing persisten t infections, Previously, we have shown that the core protein has an immuno modulatory function including the suppression of T lymphocyte responses to viral infection. To investigate the underlying mechanism for the role of co re protein in immune modulation, we examined the effect of core on the sens itivity of the human T cell line, Jurkat, to Pas-mediated apoptosis. The tr ansient and stable expression of core protein in Jurkat cells increased the sensitivity of cells to Fas-mediated apoptosis when compared to control ce lls expressing vector DNA alone. In addition, we demonstrated that the core protein binds to the cytoplasmic domain of Fas which may enhance the downs tream signaling event of Fas-mediated apoptosis. The expression of core pro tein did not alter the cell surface expression of Fas, indicating that the increased sensitivity of core-expressing cells to Fas ligand was not due to upregulation of Fas. Furthermore, we observed the augmentation of caspase- 3 activity in core-expressing cells. These results suggest that the core pr otein may promote the apoptosis of immune cells during HCV infection via th e Fas signaling pathway, thus facilitating HCV persistence. (C) 2000 Academ ic Press.