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 liver disease worldwide and is remarkably efficient at establishing persistent infections. Previously, we have shown that the core protein has an immunomodulatory function including the suppression of T lymphocyte responses to viral infection. To investigate the underlying mechanism for the role of core protein in immune modulation, we examined the effect of core on the sensitivity of the human T cell line, Jurkat, to Fas-mediated apoptosis. The transient and stable expression of core protein in Jurkat cells increased the sensitivity of cells to Fas-mediated apoptosis when compared to control cells expressing vector DNA alone. In addition, we demonstrated that the core protein binds to the cytoplasmic domain of Fas which may enhance the downstream signaling event of Fas-mediated apoptosis. The expression of core protein 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 protein may promote the apoptosis of immune cells during HCV infection via the Fas signaling pathway, thus facilitating HCV persistence.
Hahn
C S
CS
Beirne Carter Center for Immunology Research, University of Virginia, Charlottesville, Virginia 22908, USA.
Cho
Y G
YG
Kang
B S
BS
Lester
I M
IM
Hahn
Y S
YS
D015703:Antigens, CD / Q000502:physiology; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000502:physiology*; D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D019169:Jurkat Cells; D008214:Lymphocytes / Q000502:physiology*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D047888:Receptors, Tumor Necrosis Factor, Type I; D014758:Viral Core Proteins / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology*
D015703:Antigens, CD; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014758:Viral Core Proteins; D019014:fas Receptor; C069130:nucleocapsid protein, Hepatitis C virus; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases