Hepatitis C virus core protein expression in human B-cell lines does not significantly modify main proliferative and apoptosis pathways.
Hepatitis C virus (HCV) chronic infection has been associated with many lymphoproliferative disorders. Several studies performed on hepatoma and fibroblast cell lines suggest a role of the HCV core protein in activation of cellular transduction pathways that lead to cell proliferation and inhibition of apoptosis. However, no data are available concerning the effects of HCV core expression on B-lymphocyte proliferation and apoptosis. B-lymphocyte cell lines permanently expressing full-length HCV 1b core sequences isolated from chronically infected patients were established using B-cell lines at different degrees of differentiation. Clones and pools of clones permanently expressing the HCV core were selected and characterized for protein expression by Western blot and FACS. Expression of HCV core proteins did not significantly enhance cell proliferation rates under normal culture conditions or under mitogenic stimulation. Analysis of NF-kappa B, CRE, TRE and SRE pathways by luciferase reporter genes did not show a significant influence of HCV core expression on these signal transduction cascades in B-lymphocytes. The effects of HCV core on anti-IgM and anti-FAS-induced apoptosis in B-cell lines was also analysed. In this experimental model, HCV core expression did not significantly modify the apoptotic profile of the B-lymphocyte cell lines tested. These data underline a cell type-specific effect of HCV core expression. In fact, it was not possible to show a significant contribution of the HCV core protein in activation of the major B-cell signal transduction pathways involved in the regulation of proliferation and programmed cell death, which is in contrast with the results reported in hepatoma cell lines.
Giannini
Carlo
C
INSERM Unit 370, Liver Cancer and Molecular Virology, Pasteur-Necker Institutes, 156 rue de Vaugirard, 75730 Paris, France2.|Department of Internal Medicine, University of Florence, Florence, Italy1.
Caini
Patrizio
P
Department of Internal Medicine, University of Florence, Florence, Italy1.
Giannelli
Francesca
F
Department of Internal Medicine, University of Florence, Florence, Italy1.
Fontana
Francesca
F
INSERM Unit 370, Liver Cancer and Molecular Virology, Pasteur-Necker Institutes, 156 rue de Vaugirard, 75730 Paris, France2.
Kremsdorf
Dina
D
INSERM Unit 370, Liver Cancer and Molecular Virology, Pasteur-Necker Institutes, 156 rue de Vaugirard, 75730 Paris, France2.
Bréchot
Christian
C
INSERM Unit 370, Liver Cancer and Molecular Virology, Pasteur-Necker Institutes, 156 rue de Vaugirard, 75730 Paris, France2.
Zignego
Anna Linda
AL
Department of Internal Medicine, University of Florence, Florence, Italy1.
D000888:Antibodies, Anti-Idiotypic / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D058846:Antibodies, Monoclonal, Murine-Derived; D017209:Apoptosis / Q000187:drug effects; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D002455:Cell Division; D002460:Cell Line; D005434:Flow Cytometry; D006801:Humans; D014162:Transfection; D014758:Viral Core Proteins / Q000032:analysis / Q000378:metabolism*
D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D058846:Antibodies, Monoclonal, Murine-Derived; D014758:Viral Core Proteins; C411023:anti-Fas monoclonal antibody; C044203:anti-IgM; C069130:nucleocapsid protein, Hepatitis C virus