Iron enhances hepatitis C virus replication in cultured human hepatocytes

Background: Iron overload in the presence of increasing concentrations of i ron is one of the indicators of poor response to interferon therapy in chro nic hepatitis C. In order to analyze the effect of iron on hepatitis C viru s (HCV) replication, we measured replication in an HCV-infected cell line. Methods and Results: Cells from a non-neoplastic HCV-infected human hepatoc yte line (PH5CH8) susceptible to HCV infection and supportive of HCV replic ation were used in this study. The replication of HCV RNA was measured by r everse transcription-nested polymerase chain reaction (RT-nested PCR). PH5C H8 cell viability was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. PH5CH8 cells were incubated with 0, 1, 10 , 50, and 100 mu M Of FeSO4 at 37 degrees C with 5% CO2. Forty-eight hours after iron supplementation, the quantity of HCV RNA in the cells incubated in 50 and 100 mu M of FeSO4 was approximately ten times that of the cells w ith no iron supplementation. Similar changes were observed beginning at 12 h from supplementation with FeSO4 and continued for at least 72 h after sup plementation. MTT assay indicated that iron did not have cytotoxic effects on the PH5CH8 cells. Conclusion: Iron enhances HCV replication in a hepatoc yte cell line. The results suggest that iron deposition in hepatocytes coul d facilitate HCV infection in the liver.