Induction of FAS ligand expression in a human hepatoblastoma cell line by HCV core protein.
Tumour cells and virus infected cells expressing Fas ligand (FasL) can evade immune surveillance by inducing apoptosis in T cells expressing Fas. In order to characterise a possible role of hepatitis C virus (HCV) core protein in similar mechanisms during HCV infection, we investigated Fas ligand expression and activity in a human hepatoblastoma cell line (HepG2) constitutively expressing this protein. Strong FasL induction was detected by immunoblotting and flow cytometry analysis in the core expressing cell lines Hep39. In contrast, vector transfected cells or cell lines expressing HCV E1-E2 proteins did not show FasL expression. Co-cultivation experiments of Hep39 cells with a Fas-sensitive T cell line indicated that FasL induced by the core protein had apoptotic activity toward target cells. Effect of the core protein on induction of FasL promoter was further examined by co-transfection of HepG2 cells with core-bearing plasmid and a vector in which luciferase gene expression is driven by human FasL promoter. Results of the luciferase assay indicated a positive regulation of FasL promoter by the core protein. In conclusion, HCV core protein plays a role in the induction of functional FasL in hepatoblastoma cell line and apoptosis in a target T cell line expressing Fas. Similar mechanisms may contribute, in vivo, to establishment of chronic infection and development of hepatocellular carcinoma (HCC).
Laboratory of Virology, Istituto Superiore di Sanità, Viale Regina Elena 299, Rome 00161, Italy.
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Ruggieri
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Murdolo
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Rapicetta
D017209:Apoptosis; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016174:Hepacivirus; D018197:Hepatoblastoma / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D019169:Jurkat Cells; D008156:Luciferases / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics; D011401:Promoter Regions, Genetic; D014162:Transfection; D014758:Viral Core Proteins / Q000235:genetics / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus; D008156:Luciferases