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| Pathogenesis and Immunology of HCV Infection |
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Elucidation of the role of the immune response in HCV clearance or the establishment of persistent infection is a central focus of the laboratory. There are several active project areas, including establishing novel animal models for studying HCV replication and pathology and understanding the role of T cells, B cells, NK cells and different antigen-presenting cells in resolution or persistence of HCV infection. Studies designed to define the role of T-cell subsets and NK cells in the resolution of acute infection are under way in chimpanzees, the experimental model of HCV infection.
Lynn B. Dustin leads studies focused on the B-cell response and extrahepatic manifestations of HCV infection. Serum antibody levels and the levels of self-reactive autoantibodies are increased in HCV-infected patients. As many as half of all HCV patients may develop mixed cryoglobulinemia, a condition in which antibodies may precipitate in the tissues and blood vessels with detrimental consequences. In some groups of patients, HCV infection may also contribute to the development of B-cell lymphomas. It has been reported that the HCV envelope glycoprotein, E2, can bind to CD81, a molecule that is widely expressed and that, on B cells, is part of a "coreceptor" complex that regulates the threshold for activation and differentiation signals. Studies of lymphocytes from HCV-infected patients and normal controls, as well as in vitro models, are under way to learn how HCV infection affects B-lymphocyte function.
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