Abstract

The proposed research aims to elucidate unresolved features in the life cycle of HBV including the regulation of expression of the various genes and the formation of the HBV viral particles, and to further investigate HBV-associated oncogenesis. The specific issues to be addressed include 1) the role and possible independent regulation of the two surface antigen promoters, an analysis of the function of the large surface antigen product, P45, characterization of the core promoter specifically in relation to the formation of the precore and core transcripts, and the possible formation of the polymerase gene. We will also investigate the interaction of the core promoter with a contiguous pol III promoter directing the formation of an RNA from the short strand. 2) Further characterization of the HBV enhancer including fine mapping and mutational analysis, determination of its activation of the various HBV promoters and elucidation of trans-acting (liver-specific) factor responsible for enhancer activity. 3) Elucidation of the function of core structures including a) the role of precore in the formation of the e antigen, including the determination of e antigen structures; b) the role of the precore in the formation of sAg/cAg compositive structures. 4) The role of integrated HBV sequences in HCC oncogenesis. These studies involve characterization of about 20 isolated hepatitis-specific and tumor-specific genes.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37AI019744-12
Application #
3481066
Study Section
Special Emphasis Panel (NSS)
Project Start
1982-07-01
Project End
1996-04-30
Budget Start
1993-05-01
Budget End
1994-04-30
Support Year
12
Fiscal Year
1993
Total Cost
Indirect Cost

  Institution

Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143

  Publications

Cross, J C; Wen, P; Rutter, W J (1993) Transactivation by hepatitis B virus X protein is promiscuous and dependent on mitogen-activated cellular serine/threonine kinases. Proc Natl Acad Sci U S A 90:8078-82
Antonucci, T K; Rutter, W J (1989) Hepatitis B virus (HBV) promoters are regulated by the HBV enhancer in a tissue-specific manner. J Virol 63:579-83
Standring, D N; Ou, J H; Masiarz, F R et al. (1988) A signal peptide encoded within the precore region of hepatitis B virus directs the secretion of a heterogeneous population of e antigens in Xenopus oocytes. Proc Natl Acad Sci U S A 85:8405-9
Garcia, P D; Ou, J H; Rutter, W J et al. (1988) Targeting of the hepatitis B virus precore protein to the endoplasmic reticulum membrane: after signal peptide cleavage translocation can be aborted and the product released into the cytoplasm. J Cell Biol 106:1093-104
Ou, J H; Rutter, W J (1987) Regulation of secretion of the hepatitis B virus major surface antigen by the preS-1 protein. J Virol 61:782-6
Ou, J H; Yen, T S; Wang, Y F et al. (1987) Cloning and characterization of a human ribosomal protein gene with enhanced expression in fetal and neoplastic cells. Nucleic Acids Res 15:8919-34
Ou, J H; Laub, O; Rutter, W J (1986) Hepatitis B virus gene function: the precore region targets the core antigen to cellular membranes and causes the secretion of the e antigen. Proc Natl Acad Sci U S A 83:1578-82
Standring, D N; Rutter, W J (1986) The molecular analysis of hepatitis B virus. Prog Liver Dis 8:311-33
Standring, D N; Ou, J H; Rutter, W J (1986) Assembly of viral particles in Xenopus oocytes: pre-surface-antigens regulate secretion of the hepatitis B viral surface envelope particle. Proc Natl Acad Sci U S A 83:9338-42
Shaul, Y; Rutter, W J; Laub, O (1985) A human hepatitis B viral enhancer element. EMBO J 4:427-30

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