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HEPATITIS C VIRUS INFECTS THE SAME IMMUNE CELL SUBSETS IN OCCULT INFECTION AND CHRONIC HEPATITIS C BUT ITS REPLICATION IS INVERSELY CORRELATED WITH ENDOGENOUS TRANSCRIPTION OF DIFFERENT TYPES OF INTERFERONS
TNQ Pham, TI Michalak
Molecular Virology and Hepatology Research, Faculty of Medicine, Memorial University, St. John’s, Newfoundland
Infection of the lymphatic system by hepatitis C virus (HCV) appears to be an intrinsic characteristic of both chronic hepatitis C (CHC) and occult persistent HCV infection, but the subsets of immune cells involved were not defined. In the current study, we characterized HCV RNA expression and replication status in affinity-purified CD4+ and CD8+ T lymphocytes, B cells and monocytes in CHC and silent infection continuing after clinical resolution of hepatitis C. All cell subtypes investigated supported HCV replication in both forms of infection, although the extent to which different subsets were infected varied amongst the patients. HCV loads in the cells were markedly greater in CHC than in occult infection. While HCV was identified with an approximately similar frequency in all immune cell subtypes in CHC, greatest virus loads were found in monocytes. In contrast, B cells carried highest levels of HCV RNA in occult infection, while monocytes were the least frequently infected. Detection of HCV NS5A protein by confocal microscopy and unique HCV variants in immune cells by clonal sequencing confirmed active virus replication in different immune cell types. In addition, HCV replication in CD4+ and CD8+ T lymphocytes and in total PBMC can be completely inhibited by interferon-alpha (IFNalpha) in low-level (occult) HCV infection and by IFNgamma in CHC. This study provides definitive proof that the immune system supports HCV replication regardless of the clinical appearance of HCV infection, identifies for the first time the immune cell types which are virus reservoirs in these two distinctive forms of HCV persistence, and recognizes a potential contribution of IFNs to control of HCV replication in T lymphocytes.