The candidate's immediate career goals are to enhance his own skills and research capabilities and to develop an efficient, productive research group, capable of contributing significantly to the understanding of hepatitis B virus (HBV) and the diseases it causes. Attainment of these goals is important for his development as an independent investigator and should lead to an enhancement of his position in the scientific community as well as to promotion and tenure at Rush. The candidate's long-term career goals are to make solid scientific contributions to the study of HBV, enabling the maintenance of a stable, funded laboratory. While continuing along productive lines of investigation, he hopes to remain open to new promising lines of investigations in the virology of HBV, in multi-disciplinary approaches to HBV, and in new promising areas. This Research Career Development Award will allow the candidate to concentrate on the research aspects of his career by decreasing his teaching and administrative duties. It will also allow him to learn specific new skills during a sabbatical year. The work proposed by the candidate primarily involves the identification and characterization of the HBV receptor on hepatocytes. The approach is based on the candidate's discovery that recombinant hepatitis B surface antigen particles containing the large S protein of HBV, but not those lacking the large S protein, are capable of attaching to human liver-derived plasma membranes and to human hepatoma-derived cell lines. The biochemical nature of the large S protein receptor on the HepG2 hepatoma cell line will first be determined by treatment of HepG2 cells with degradative enzymes. The molecular weight of the receptor will be determined by using the large S particles as a probe for blotting separated plasma membranes proteins and for isolating a receptor-ligand complex. Antibodies to the receptor molecule will be generated by an anti-idiotype scheme or as monoclonal antibodies which bind to the surface of HepG2 cells and prevent large S particles from binding. Such anti-receptor antibodies will be valuable in identifying and characterizing the HBV receptor, and might lead to a therapy for chronic HBV infection, as mentioned above. All of the blocking peptides and antibodies described above will be used to confirm that the infectious HBV particles use the same receptor thereby validating its potential as a target for therapy.
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| Komai, K; Peeples, M E (1990) Physiology and function of the vero cell receptor for the hepatitis B virus small S protein. Virology 177:332-8 |
| Pontisso, P; Petit, M A; Bankowski, M J et al. (1989) Human liver plasma membranes contain receptors for the hepatitis B virus pre-S1 region and, via polymerized human serum albumin, for the pre-S2 region. J Virol 63:1981-8 |
