# PATHOGENESIS OF LIVER DISEASE IN HEPATITIS

> **NIH NIH R01** · SCRIPPS RESEARCH INSTITUTE, THE · 1990 · $275,428

## Abstract

The mechanism(s) responsible for hepatocellular injury and malignant
transformation following hepatitis B virus (HBV) infection are entirely
unknown.  Since HBV infection is not directly cytopathic for hepatocytes,
the dominant current hypothesis proposes that the cellular immune response
destroys infected hepatocytes that express one or more virus encoded
antigens on their surface in the context of autologous HLA determinants.
This hypothesis has not been testable due to the unavailability of human
target cells that co-express the necessary viral and histocompatibility
antigens required for a definitive study of antigen specific, HLA
restricted T cell mediated cytotoxicity in this disease.  Our long term
programmatic objective is to test the above hypothesis.  Thus, we have
developed the technology necessary to produce high level expression of HBV
encoded antigens at high efficiency in primary human cell lines of defined
HLA phenotype.  Using recombinant retroviral, vaccinia and Epstein-Barr
virus based expression vectors we are able to express several of the HBV
gene products in primary human cells.  We have shown that antigens so
produced and expressed are recognizable by lymphocytes sensitized in vivo
during natural HBV infection.  We have also crated the organizational
framework necessary for the identification and recruitment of large numbers
of patients with acute and chronic hepatitis B virus infection who will
provide the materials needed to analyze the peripheral and intrahepatic
cellular immune response to HBV.  Particular emphasis will be placed on
assessment of the prevalence, phenotype, function and antigenic fine
specificity of HBV specific cytotoxic T cell lines and clones established
in response to cell associated HBV antigens expressed by autologous cell
lines engineered to contain our recombinant expression vectors.  These
results will be correlated with clinical and biochemical parameters of
disease activity to examine the possibility of a causal relationship
between the two.  The results of these studies will elucidate the
immunopathogenetic mechanisms responsible for viral clearance and liver
cell injury in HBV infection and should also have significant implications
for advanced vaccine development and, perhaps, specific immunotherapy of
the chronic carrier state, as well.

## Key facts

- **NIH application ID:** 3129460
- **Project number:** 2R01AI020001-07A1
- **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:** 1990
- **Award amount:** $275,428
- **Award type:** 2
- **Project period:** 1983-07-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3129460

## Citation

> US National Institutes of Health, RePORTER application 3129460, PATHOGENESIS OF LIVER DISEASE IN HEPATITIS (2R01AI020001-07A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3129460. Licensed CC0.

---

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