Activation of Intracellular MAPK/ERK Initiated by Hepatitis C Virus Envelope Protein E2 in HepG2 Cells

CD81, widely expressed on the surface of various human cells including hepatocytes, is a protein involved in intracellular signal transduction pathways. Recent studies suggested that human CD81 could specifically interact with hepatitis C virus (HCV) envelope protein E2. Therefore, CD81 has been identified as a putative cellular receptor for HCV. The HCV E2-CD81 interaction was considered a molecular mechanism contributing to HCV infection and pathogenicity. MAPK/ERK is characteristically associated with cell proliferation and hypertrophy. To investigate the effect of HCV on MAPK/ERK, human HepG2 cells were used in this study. CD81 expression on HepG2 cell surface was determined by flow cytometry with method of immunofluorescence. The cells were cultured in DMEM medium without fetal calf serum for 7 h, and then treated with HCV E2 protein at different time courses. Activation of MAPK/ERK in the cells was measured by Western blot, immunohistochemical and immunofluorescent analyses. Phosphorylation of MAPK/ERK was related to the concentration of HCV E2 proteins and to the time length of stimulation. MAPK/ERK in HepG2 cells was activated by HCV E2 protein, suggesting that HCV E2-CD81 interaction might be involved in intracellular signal transduction and might play an active role in HCV pathogenicity.