Replication of hepatitis C virus in peripheral blood mononuclear cells. Effect of alpha-interferon therapy

Hepatitis C virus (HCV) is a positive-stranded RNA virus which replicates through a negative-stranded RNA intermediate. Using a PCR procedure to detect positive and negative strands, we investigated the existence of HCV replication in lymphoid cells. Both positive and negative strands were found in the peripheral blood mononuclear cells (PBMC) of all patients (n = 10) with untreated chronic hepatitis C. No HCV sequences were detected in PBMC in any of the 8 healthy controls. Fifteen patients with chronic hepatitis C were studied at the end of a 12-month course of alpha-interferon therapy. The positive strand was detected in PBMC in all 9 non-responder patients, and the negative strand in 7. In contrast, in PBMC from responder patients (n = 6) the positive strand was found in 4 and the negative strand in only 2 cases. These results demonstrate that HCV can infect PBMC and replicate in these cells and that interferon seems to exert an inhibitory effect on this process. Persistence of HCV-RNA in PBMC may help explain disease relapse after successful interferon therapy.