# STUDIES ON THE REPLICATION AND ONCOGENICITY OF HBV

> **NIH NIH R01** · MOUNT SINAI SCHOOL OF MEDICINE OF CUNY · 1987 · $98,400

## Abstract

There are an estimated 176 million chronic carriers of hepatitis B virus
(HBV) world wide and strong epidiomological evidence linking the carrier
state with development of hepatocellular carcinoma.  Thus, it is of utmost
importance to have in vitro systems available for studying viral
replication and for elucidating the mechanism(s) by which HBV infected
cells become malignantly transformed.  Although it has been possible to
obtain partial expression of viral functions by transfecting rodent cells
with cloned HBV DNA, these cells do not support efficient viral replication
nor do they become malignantly transformed.  Nevertheless, cloned HBV DNA
is capable of causing hepatitis in chimpanzees.  The working hypothesis for
the experiments proposed here is that the relatively weak promoters
associated with HBV genes other than the gene coding for the surface
antigen of the virus cannot overcome host and/or tissue specific
restrictions imposed by rodent cells or cells of non-hepatic origin.  Thus,
to meet our long-term goal of establishing in vitro systems for studying
HBV, we propose 1) to obtain increased expression of viral genes in mouse
lines that already carry integrated HBV genes by a) treating them with
compounds known to enhance expression of integrated viral genomes; b)
exposing them to tumor promoters and subeffective doses of physical and
chemical carcinogens and c) by "superinfecting" them with additional
recircularized HBV genomes or with new hybrid plasmids in which the viral
genome is linked to strong promoters or enhancing sequences; 2) to develop
hybrid plasmids designed to replicate episomally in simian cells or to give
efficient expression of viral functions in cultured hepatocytes; 3) to
create transgenic mice carrying HBV sequences by introducing recircularized
HBV genomes or hybrid plasmids with HBV sequences linked to strong
promoters into mouse embryo cells; 4) to develop methods of in situ
hybridization suitable for use with biopsy material which will allow
association of HBV gene expression with various clinical stages of chronic
liver disease.  These studies should elucidate at least some of the factors
that regulate expression of HBV genes in cultured cells, in transgenic mice
and in the liver of infected individuals.

## Key facts

- **NIH application ID:** 3172651
- **Project number:** 3R01CA034818-03S1
- **Recipient organization:** MOUNT SINAI SCHOOL OF MEDICINE OF CUNY
- **Principal Investigator:** GEORGE ACS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $98,400
- **Award type:** 3
- **Project period:** 1984-03-15 → 1987-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172651

## Citation

> US National Institutes of Health, RePORTER application 3172651, STUDIES ON THE REPLICATION AND ONCOGENICITY OF HBV (3R01CA034818-03S1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172651. Licensed CC0.

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