Hepadnaviruses are small, hepatotropic DNA viruses that can persistently infect the liver of a variety of animal hosts, including humans, and cause disease. There is a close association between chronic HBV infection and the development of hepatocellular carcinoma (HCC). Active viral replication is necessary for HCC and other hepadnavirus-associated diseases. Although they have DNA genomes, hepadnaviruses replicate via reverse transcription of an RNA intermediate (RNA pregenome) resulting in a relaxed circular DNA genome. Integral to reverse transcription are the specific initiation or priming events leading to successful minus and plus strand DNA synthesis. The focus of the proposed research is understand the initiation and elongation of minus and plus strand DNA synthesis. This will be done by defining and characterizing the cis- acting elements on the genome involved in minus and plus strand DNA synthesis and by defining and characterizing the viral trans factors (the C and P proteins) that interact with these cis-acting elements during reverse transcription. Genetic and biochemical approaches will be undertaken to achieve our specific aims.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
First Independent Research Support & Transition (FIRST) Awards (R29)
Project #
5R29GM050263-04
Application #
2022791
Study Section
Experimental Virology Study Section (EVR)
Project Start
1994-01-01
Project End
1998-12-31
Budget Start
1997-01-01
Budget End
1997-12-31
Support Year
4
Fiscal Year
1997
Total Cost
Indirect Cost
Name
University of Wisconsin Madison
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715
Liu, Ning; Tian, Ru; Loeb, Daniel D (2003) Base pairing among three cis-acting sequences contributes to template switching during hepadnavirus reverse transcription. Proc Natl Acad Sci U S A 100:1984-9
Mueller-Hill, Karlyn; Loeb, Daniel D (2002) cis-Acting sequences 5E, M, and 3E interact to contribute to primer translocation and circularization during reverse transcription of avian hepadnavirus DNA. J Virol 76:4260-6
Loeb, Daniel D; Mack, Amanda A; Tian, Ru (2002) A secondary structure that contains the 5' and 3' splice sites suppresses splicing of duck hepatitis B virus pregenomic RNA. J Virol 76:10195-202
Havert, Michael B; Ji, Lin; Loeb, Daniel D (2002) Analysis of duck hepatitis B virus reverse transcription indicates a common mechanism for the two template switches during plus-strand DNA synthesis. J Virol 76:2763-9
Loeb, D D; Tian, R (2001) Mutations that increase in situ priming also decrease circularization for duck hepatitis B virus. J Virol 75:6492-7
Loeb, D D; Tian, R; Gulya, K J et al. (1998) Changing the site of initiation of plus-strand DNA synthesis inhibits the subsequent template switch during replication of a hepadnavirus. J Virol 72:6565-73
Jiang, H; Loeb, D D (1997) Insertions within epsilon affect synthesis of minus-strand DNA before the template switch for duck hepatitis B virus. J Virol 71:5345-54
Loeb, D D; Gulya, K J; Tian, R (1997) Sequence identity of the terminal redundancies on the minus-strand DNA template is necessary but not sufficient for the template switch during hepadnavirus plus-strand DNA synthesis. J Virol 71:152-60
Havert, M B; Loeb, D D (1997) cis-Acting sequences in addition to donor and acceptor sites are required for template switching during synthesis of plus-strand DNA for duck hepatitis B virus. J Virol 71:5336-44
Mueller-Hill, K; Loeb, D D (1996) Previously unsuspected cis-acting sequences for DNA replication revealed by characterization of a chimeric heron/duck hepatitis B virus. J Virol 70:8310-7

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