# HEPATITIS B VIRUS/CHRONIC HEPATITIS/LIVER CANCER

> **NIH NIH R01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 1988 · $271,291

## Abstract

Our overall goal is to study regulation of hepatitis B virus (HBV)
gene expression and events in virus replication in human, animal
model and cell culture systems and to investigate mechanisms
whereby persistent infection with hepatitis B virus causes chronic
liver disease and leads to development of primary hepatocellular
carcinoma.  Our basic premise is that HBV genetic elements
and/or specific viral gene products (regulatory or structural) by
virtue of their direct function or a separate effect on host cell
gene expression cause pathophysiologic consequences leading to
chronic liver disease and/or hepatocyte transformation.  Our
specific aims will be (1) to study changes in HBV gene expression
and/or genome replication which occur during persistent viral
infection and to relate these changes to abnormalities in the virus
assembly/secretion mechanism, (2) to study molecular forms of
HBV genomes accumulating in liver during persistent infection
and how these molecular forms and their accumulation might
relate to the mechanism of hepatic oncogenesis, (3) to study cis
and trans acting regulatory elements in the HBV genome and how
these elements control HBV gene expression, (4) to determine
whether factors which modify the function of HBV regulatory
elements in cell culture systems influence HBV gene expression in
vivo, and (5) to study how the HBV genome, its regulatory
elements or gene products might interact with, modify expression
of, or work in concert with cellular oncogenes or growth factors
to alter growth of liver and/or other cells in culture.  Specific
experiments will utilize valuable tissue samples from So. African
blacks with liver cancer who show an apparent defect in the virus
replication/assembly/secretion pathway as well as tissues from
Greek patients with replicative vs. non-replicative infection, and
will use molecular hybridization, cloning and immunologic
methods to characterize HBV molecules, viral proteins and viral
particles accumlating in these tissues.  Other experiments will use
plasmid expression vectors (CAT) and DNA transfection methods
to study regulatory elements in the HBV genome, transgenic mice,
containing all or part of the HBV genome in a form expressable in
a liver tissue specific manner to study tissue specific regulation in
an in vivo model and factors (such as glucocorticoids, interferon,
hepatotoxins and chemical carcinogens) which might modify HBV
gene expression, and cell culture systems to study the role of HBV
and other genes in causing immortalization and/or further
transformation of hepatocytes or other eukaryotic cells.  By this
multifaceted approach, using modern molecular and cellular
methods, we hope to gain further understanding of the possible
role of HBV in chronic liver disease and primary liver cancer.

## Key facts

- **NIH application ID:** 3170510
- **Project number:** 5R01CA032605-07
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** DAVID A SHAFRITZ
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $271,291
- **Award type:** 5
- **Project period:** 1982-02-01 → 1992-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170510

## Citation

> US National Institutes of Health, RePORTER application 3170510, HEPATITIS B VIRUS/CHRONIC HEPATITIS/LIVER CANCER (5R01CA032605-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170510. Licensed CC0.

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