TRANSFUSION RELATED VIRAL INFECTIONS AND IMMUNE RESPONSE

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The theme focuses on viral infections and immune responses associated with transfusion of blood. An integrated program of 7 basic and clinical research projects, aided by two specialized core units, is designed to investigate the contemporary problems of transfusion-transmitted hepatitis, CMV, and AIDS, and resulting effects on the immune system. The molecular mechanisms of pathogenesis of post-transfusion hepatitis caused by hepatitis viruses as well as the non-A, non-B viruses are to be investigated through prospective studies in transfused patients and experimental studies in animal models which will also be used in study of antiviral agents against hepatotropic viruses (Projects 1 and 2). Immunologic mechanisms in post-transfusion CMV infection, in donor-specific transfusions prior to renal transplantation and immunosuppressive effects per se of homologous versus autologous blood transfusions will be studied in Projects 3, 4 and 5. The problems of transfusion-associated AIDS are addressed in culturing the virus for definition of infection versus immunity to the virus in antibody positive blood donors (project 6) and in deriving animal models for therapeutic and preventive measures against the AIDS retrovirus (ARV/LAV/HTLV III) infection (project 7). The specific expertise in viral immunology, molecular hybridization analyses with cloned DNA probes, flow-cytometry for cell-surface marker analyses with monoclonal antibodies and cell sorting in experimental cell biology studies are made available to all investigators by the Core Units A and B. The ultimate goal is to prevent transmission of the blood borne viral infection and managing the unresolved infection with antiviral therapy. This goal will be achieved by promoting interaction between the investigators and by using the clinical resources of the University of California Hospitals, the Mount Zion Medical Center and the Irwin Memorial Blood Bank in San Francisco. The program complements and strengthens the academic commitment of UCSF faculty to excellence in teaching, research and service in transfusion medicine.