HEPATITIS-C VIRUS-RNA IN DIFFERENT BLOOD LYMPHOCYTE SUBSETS

Objective: Lymphocytes play an important role in the pathogenesis of chronic viral hepatitis. Apart from intrahepatic replication of hepatitis C virus (HCV), there is also strong evidence for an extrahepatic site in mononuclear blood cells. To further characterize the site of HCV replication, we tested resting peripheral blood lymphocytes (PBL) and stimulated PBL for the presence of positive- and negative-stranded HCV RNA. Method: PBL from 10 patients with histologically proven chronic active hepatitis C were sorted into CD4+ (T helper) and CD8+ (T suppressor) T cells, CD20+ B cells and CD16+ natural killer (NK) cells by a fluorescence-activated cell sorter. Results: HCV RNA was detected by a nested polymerase chain reaction. Positive-standed HCV RNA was present in all 10 sera. Resting B and NK cells were positive in eight out of 10, CD4+ T cells in six out of 10 and in CD8+ T cells in five out of 10 patients for positive-stranded, but negative for negative-stranded HCV RNA. The supernatants were all negative for HCV RNA. In addition, we looked for positive- and negative-stranded HCV RNA in serum, resting PBL, Epstein-Barr virus transformed B cell lines and phytohaemagglutinin-stimulated T cells from two patients with chronic HCV infection. Positive-standed HCV RNA was present in both sera but only in one resting lymphocyte group. Negative-stranded HCV RNA could not be detected in sera nor in the resting lymphocyte group. After stimulation, however, negative-stranded HCV RNA was present-in both Epstein-Barr virus transformed B cell lines as well as in phytohaemagglutinin-stimulated T cells. Conclusions: We conclude that PBL from HCV-infected patients are also infected with this virus. The predominant sites of HCV are B and NK cells. These cells may, therefore, represent a reservoir for hepatitis C virions. According to our results viral replication occurs in B and probably in T cells.