# PATHOGENESIS OF LIVER DISEASE IN HEPATITIS

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1993 · $377,751

## Abstract

The hepatitis B virus (HBV) is a small, enveloped hepatotropic virus with
a double stranded DNA genome that causes acute and chronic
necroinflammatory liver disease (hepatitis) and hepatocellular carcinoma.
Since HBV is not directly cytopathic for the infected hepatocyte, the
cellular immune response to HBV encoded antigens is thought to be
responsible for the liver disease caused by HBV, and to play an important
role in viral clearance as well.  Because HLA class I restricted, CD8-
positive cytotoxic T lymphocytes (CTL) are known to interact directly
with processed viral peptides at the cell surface, we have proposed that
they play a direct role in viral clearance by destroying infected cells,
and possibly by non-cytolytic anti-viral mechanisms as well.  During the
past several years we established the necessary models and technology to
test this hypothesis.  In a recent series of studies, we demonstrated
that patients with acute viral hepatitis who eventually clear the virus
develop a polyclonal, HLA class I restricted, CD-8 positive CTL response
to multiple HBV encoded antigens, but that this response is not
detectable in patients with chronic HBV infection.  We now propose to
define the molecular and cellular characteristics of the HBV specific CTL
response during acute and chronic viral hepatitis, and to determine the
role it plays in viral clearance and liver cell injury.  A desired by-
produce of this research may be the rational design of CTL-based
therapeutic strategies to terminate persistent HBV infection, thereby
reducing the human and economic toll of chronic liver disease and
hepatocellular carcinoma in the 300 million chronic HBV carriers alive
throughout the world today.  Because of the power of the technology we
have developed, the same strategy can be applied to study the CTL
response to any human pathogen whose genome has been cloned and
sequenced.

## Key facts

- **NIH application ID:** 3129461
- **Project number:** 2R01AI020001-10
- **Recipient organization:** SCRIPPS RESEARCH INSTITUTE, THE
- **SAM.gov UEI:** PHZJFZ32NKH4
- **Principal Investigator:** FRANCIS VINCENT CHISARI
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $377,751
- **Award type:** 2
- **Project period:** 1983-07-01 → 1998-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129461

## Citation

> US National Institutes of Health, RePORTER application 3129461, PATHOGENESIS OF LIVER DISEASE IN HEPATITIS (2R01AI020001-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129461. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*