Hepatitis C virus core protein induces expression of genes regulating immune evasion and anti-apoptosis in hepatocytes.
Hepatitis C virus (HCV) Core protein is implicated in the development of hepatocellular carcinoma (HCC). We utilized a HepG2 human hepatocyte cell line with inducible expression of HCV Core protein (HCV-1b) to investigate the early effects of Core protein on hepatocyte gene expression and to identify molecular processes modulated by the Core protein. A significant change was observed in the expression of 407 genes, which included genes regulating apoptosis, immune response, and cell cycle. Some of these genes were previously known to be tumor markers. The decreased expression of chemo-attractants such as TNFSF10, CCL20, and osteopontin was observed, which suggested that HCV Core expression could lead to suppression of inflammatory response as well as trafficking of macrophages and neutrophils to the site of HCV infection. An increased expression of anti-apoptosis factors including PAK2, API5, BH1, Tax1BP1, DAXX, and TNFAIP3/A20 was observed. Some of these genes were also linked to the regulation of NFKB activation and that the alteration of their expression levels, by HCV Core, might lead to the suppression NFKB activation of inflammatory responses. Our data suggested that Core expression may contribute to the viral persistence by protecting infected hepatocytes from cell death by the suppressing apoptosis and inflammatory reaction to HCV viral infection.
Nguyen
Hau
H
Department of Medical Microbiology and Immunology, School of Medicine, Topper Hall, Room 3146, University of California, Davis, CA 95616, USA.
Sankaran
Sumathi
S
Dandekar
Satya
S
D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000276:immunology*; D022781:Hepatocytes / Q000502:physiology* / Q000821:virology*; D006801:Humans; D007108:Immune Tolerance / Q000235:genetics; D007113:Immunity, Innate / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D014758:Viral Core Proteins / Q000502:physiology*
D014408:Biomarkers, Tumor; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus