HEPATITIS-C VIRUS-RNA IN DIFFERENT BLOOD LYMPHOCYTE SUBSETS

Objective: Lymphocytes play an important role in the pathogenesis of c hronic viral hepatitis. Apart from intrahepatic replication of hepatit is C virus (HCV), there is also strong evidence for an extrahepatic si te 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 HC V RNA. Method: PBL from 10 patients with histologically proven chronic active hepatitis C were sorted into CD4+ (T helper) and CD8+ (T suppr essor) 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 prese nt in all 10 sera. Resting B and NK cells were positive in eight out o f 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, resti ng PBL, Epstein-Barr virus transformed B cell lines and phytohaemagglu tinin-stimulated T cells from two patients with chronic HCV infection. Positive-standed HCV RNA was present in both sera but only in one res ting lymphocyte group. Negative-stranded HCV RNA could not be detected in sera nor in the resting lymphocyte group. After stimulation, howev er, negative-stranded HCV RNA was present-in both Epstein-Barr virus t ransformed B cell lines as well as in phytohaemagglutinin-stimulated T cells. Conclusions: We conclude that PBL from HCV-infected patients a re also infected with this virus. The predominant sites of HCV are B a nd NK cells. These cells may, therefore, represent a reservoir for hep atitis C virions. According to our results viral replication occurs in B and probably in T cells.