STRUCTURE OF HEPATITIS B CORE AND E PROTEINS

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The overall goal of this project is to elucidate the structural basis for the antigenic differences between the hepatitis B core (HBcAg) and Hepatitis B e (HBeAg) antigens. These antigens are part of a complex system of Hepatitis B viral antigens and host antibodies which characterize human infection by this virus. The presence of these antigens and anti-bodies are widely used for diagnosis of infection and also for prognosis of the disease. HBeAg protein, shares most of its amino acid sequence with the HBcAg, and yet is antigenically distinct. Such antigenic differences must reflect protein structural differences. Although the function of HBeAg during the disease is unknown, it has been recently suggested that it may play a role in the development of chronic infection during neonatal infection. A more detailed understanding of the structure of this protein may provide better insight into its function. The structural and antigenic relationship between these two proteins will be investigated using Saccharomyces cerevisiae expression systems. Two different expression vectors will be used. One directs synthesis and intra-cellular accumulation of the protein while the other carries out synthesis and secretion of the protein. Proteins corresponding to the HBCAG, HBeAg and mutants of these will be produced and purified from each of these systems and subjected to physical, chemical, and immunochemical analysis. These studies will allow us to determine the role of the environment (intracellular vs extracellular) on the physical and antigenic structure of these proteins.