Hepatitis B virus (HBV) infections are usually associated with mild and transient bone marrow depression. Rarely, aplastic anemia results. Data from my laboratory have demonstrated that HBV inhibits in a dose dependent manner the differentiation in culture of human erythroid, granulocytic, monocytic, and lymphocytic progenitor cells. HBV associated antigens and DNA can be detected in these cells after incubation with HBV in culture. In vitro exposure of human monocytes to HBV affects macrophage functions such as interleukin-1 release and the secretion of an immunosuppressive substance by these cells. Based on these observations, in vitro models to study mechanisms by which HBV suppresses human bone marrow differentiation and human macrophage function will be established. These models will be used to study HBV infection in vitro. These studies may provide means to assess in vitro parameters needed for immunoprophylaxis and antiviral therapy of HBV infection. The candidate completed an MD, PhD prior to his training in internal medicine and gastroenterology. His thesis work was in immunogenetics and immunochemistry. Since his clinical training, Dr. Zeldis has been endeavoring to perform basic investigations on the effects of HBV on the hematopoietic system. This has necessitated his learning the modern molecular biology, cellular biology, virology, and immunology. Dr. Essex of the Harvard School of Public Health is an acknowledged leader in investigations of oncogenic viruses and viruses that affect the immune system. His laboratory is actively performing investigations on the role of HBV on the hematopoietic system. Drs. Steinberg, Knudsen, and Crumpacker of the Beth Israel Hospital and Harvard Medical School also have active interests in this area. Dr. Essex's sponsorship, as well as that of the surrounding investigators at the Beth Israel Hospital and Harvard Medical School should provide an excellent environment for the candidate's studies and development.
