# MOLECULAR BASIS FOR CHRONIC HEPADNAVIRAL INFECTIONS

> **NIH NIH R01** · RESEARCH INST OF FOX CHASE CAN CTR · 1991 · $340,134

## Abstract

Hepadnaviruses can cause chronic, productive, infections, associated with
both progressive liver damage and the accumulation of aberrant,
integrated forms of viral DNA. Both events appear to be co-factors in the
development of hepatocellular carcinoma, which occurs with high frequency
in chronically-infected individuals. The productive phase of hepadnavirus
infections is apparently maintained solely by the transcriptional
activity of a covalently-closed, circular (CCC) viral DNA found at low
copy number in the nucleus of infected hepatocytes. Effective antiviral
chemotherapies to eliminate this species, by ending virus production,
should not only stop further liver damage but, also, substantially reduce
the life-time risk of liver cancer. The possibility of devising such
virus-specific therapies is encouraged by a recent report that, in duck
hepatocyte tissue culture, hepadnavirus CCC DNA is synthesized via a
virus-specified mechanism, involving reverse transcription of a viral
RNA, and not by host-specific, semi-conservation replication. A detailed
understanding of this process, including its role and significance in in
vivo virus replication will, therefore, be a major goal of our
investigations.

The process of formation and of maintenance of CCC viral DNA in chronic,
hepadnavirus infections will be studied, primary, in the context of both
in vivo and in vitro infections by duck hepatits virus. Questions to be
addressed will include: (1) What are the roles of viral and cellular
proteins in the conversion of virion, relaxed circular, partially double-
stranded DNA to CCC DNA? (2) How is CCC DNA maintained during chronic,
hepatocellular infections? (3) What is the detailed molecular mechanism
of viral DNA synthesis during chronic infections?

Towards these goals, we have identified major events in hepadnaviral DNA
synthesis and developed the first detailed model for this process,
obtained preliminary evidence that CCC DNA can accumulate, in vitro, via
an intracellular route, identified a number of drugs that appear to be
useful for characterization of the hepadnavirus life cycle, and
established a system for in vitro infection of primary woodchuck
hepatocytes with woodchuck hepatitis virus.

## Key facts

- **NIH application ID:** 3128087
- **Project number:** 5R01AI018641-10
- **Recipient organization:** RESEARCH INST OF FOX CHASE CAN CTR
- **SAM.gov UEI:** FF1XVJMDYVR1
- **Principal Investigator:** William Mason
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $340,134
- **Award type:** 5
- **Project period:** 1982-09-01 → 1994-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3128087

## Citation

> US National Institutes of Health, RePORTER application 3128087, MOLECULAR BASIS FOR CHRONIC HEPADNAVIRAL INFECTIONS (5R01AI018641-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3128087. Licensed CC0.

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