OBJECTIVE: To explore the role of the infection of monouclear cells by hepatitis C virus(HCV) in the chronicity of HCV infection. METHODS: Direct sequencing of the amplified hypervariable region (HVR) gene of HCV was used to distinguish main HCV quasispecies infecting non-hepatocytes from those infecting hepatocytes and circulating virions. The main HCV quasispecies in peripheral blood mononuclear cells(PBMC), liver-associated mononuclear cells (LAMC), serum and liver samples from 6 patients with chronic hepatitis C and from 6 patients with HCV-related cirrhosis were analysed and compared. RESULTS: The main HCV qusispecies in the livers were different from those in PBMC in 3 transplanted cirrhotic patients and 5 patients with chronic hepatitis C. Different substitutions existed between PBMC and LAMC in 3 of 6 patients analysed. Mutations were observed within the first 50 amino acids of E2 gene, which induced amino acid change in 6 of 9 patients analysed. CONCLUSION: In chronically infected patients, the detection of HCV RNA in mononuclear cells is not due to the adsorption of circulating virions but a significant infection. The compartmental distribution of HCV quasispecies in hepatocytes and mononuclear cells could be involved in the chronicity of HCV infection.
OBJECTIVE: To explore the role of the infection of monouclear cells by hepatitis C virus(HCV) in the chronicity of HCV infection. METHODS: Direct sequencing of the amplified hypervariable region (HVR) gene of HCV was used to distinguish main HCV quasispecies infecting non-hepatocytes from those infecting hepatocytes and circulating virions. The main HCV quasispecies in peripheral blood mononuclear cells(PBMC), liver-associated mononuclear cells (LAMC), serum and liver samples from 6 patients with chronic hepatitis C and from 6 patients with HCV-related cirrhosis were analysed and compared. RESULTS: The main HCV qusispecies in the livers were different from those in PBMC in 3 transplanted cirrhotic patients and 5 patients with chronic hepatitis C. Different substitutions existed between PBMC and LAMC in 3 of 6 patients analysed. Mutations were observed within the first 50 amino acids of E2 gene, which induced amino acid change in 6 of 9 patients analysed. CONCLUSION: In chronically infectedpatients, the detection of HCV RNA in mononuclear cells is not due to the adsorption of circulating virions but a significant infection. The compartmental distribution of HCV quasispecies in hepatocytes and mononuclear cells could be involved in the chronicity of HCV infection.