DETECTION OF HEPATITIS C VIRUS-SPECIFIC REPLICATION MARKERS IN PERIPHERAL BLOOD MONONUCLEARS FROM THE PATIENTS WITH CHRONIC HEPATITIS C

Abstract. The aim of present study was to evaluate a role of peripheral blood mononuclear cell (PBMC) infection with hepatitis C virus (HCV) in chronic hepatitis C (CHC) progression under experimental conditions. To this purpose, structural core-protein and nonstructural proteins of viral replication complex, as well as genomic and replicative RNA chains were determined in PBMCs of CHC patients. Blood samples were analyzed from 83 patients at different stages of the disease. Viral proteins were identified in PBMC by cytochemical staining and flow cytometry using 17 monoclonal antibodies. Genomic and replicative HCV RNA chains were detected by means of RT-PCR. HCV proteins were present in PBMC of 86% patients, the occurrence of NS5A protein being the highest. Viral proteins were located exclusively in cytoplasm of the blood cells, predominantly, monocytes, the number of HCV-positive lymphocytes being much lower. Genomic and replicative HCV RNA chains were detected in 95 and 51% patients, respectively. A statistically significant positive correlation was revealed between accumulation of viral proteins in PBMCs, and CHC progression estimated on the basis of alanine aminotransferase level, histological activity index, and degree of liver fibrosis. In majority of the patients, an imbalance in lymphocyte-to-monocyte ratio was shown. Accumulation of HCV proteins in PBMCs exhibited a statistically significant correlation with a decrease in total number of mononuclears. The data obtained suggest that PBMCs are a site of active viral replication, which may cause immune disorders and result into more severe clinical course of CHC. (Med. Immunol., vol. 10, N 4-5, pp 397-404).

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