Infection with hepatitis B virus may result in cirrhosis and has also been linked to hepatoma, one of the most common cancers worldwide. Infection with this virus is also marked by the copious production of subviral lipoprotein particles which are highly immunogenic yet non-infectious.
Our aims are twofold in scope: 1) to further dissect the assembly of subviral particles containing HBsAg, to enhance our understanding of the more complex process of virion assembly; and 2) to successfully for immunogenic chimeric subviral particles containing foreign epitopes. Specifically, three approaches will be taken. First, intermediates in the assembly pathway will be further defined. Second, the functional domains which direct the assembly process will be investigated by introducing deletion and linker-insertion mutations into both unknown signal sequences, the third hydrophobic domain, and other sites throughout the S gene. Biochemical assays developed earlier will be used to trace the natural mutant gene products to determine the locus of blocks in assembly. Third, hybrid proteins resulting from fusions or insertions of foreign sequences into either the S or pre-S2 coding region will be produced with the aim of producing fully-formed intra- or extracellular chimeric particles. Such chimeric particles may serve as the basis for a new generation of recombinant HBV-based vaccines.
