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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Physician Scientist Award (K11)
Project #
5K11AI000951-05
Application #
2056982
Study Section
Microbiology and Infectious Diseases B Subcommittee (MID)
Project Start
1990-07-01
Project End
1995-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
5
Fiscal Year
1994
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Microbiology/Immun/Virology
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143