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.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HL001917-05
Application #
3082321
Study Section
Research Manpower Review Committee (MR)
Project Start
1988-09-01
Project End
1992-08-31
Budget Start
1991-09-01
Budget End
1992-08-31
Support Year
5
Fiscal Year
1991
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
Bouffard, P; Mamish, D; Baginski, I et al. (1993) Infection of a leukemic cell line (K562) by hepatitis B virus induces cell growth inhibition. J Hepatol 17:384-9
Zeldis, J B; Jain, S; Kuramoto, I K et al. (1992) Seroepidemiology of viral infections among intravenous drug users in northern California. West J Med 156:30-5
Bouffard, P; Hayashi, P H; Acevedo, R et al. (1992) Hepatitis C virus is detected in a monocyte/macrophage subpopulation of peripheral blood mononuclear cells of infected patients. J Infect Dis 166:1276-80
Steinberg, H S; Bouffard, P; Trepo, C et al. (1990) In vitro inhibition of hemopoietic cell line growth by hepatitis B virus. J Virol 64:2577-81
Zeldis, J B; Boender, P J; Hellings, J A et al. (1989) Inhibition of human hemopoiesis by non-A, non-B hepatitis virus. J Med Virol 27:34-8
Zeldis, J B; Lee, J H; Mamish, D et al. (1989) Direct method for detecting small quantities of hepatitis B virus DNA in serum and plasma using the polymerase chain reaction. J Clin Invest 84:1503-8
Zeldis, J B; Farraye, F A; Steinberg, H N (1988) In vitro hepatitis B virus suppression of erythropoiesis is dependent on the multiplicity of infection and is reversible with anti-HBs antibodies. Hepatology 8:755-9