# In search of an HBV cure: novel model systems and targets

> **NIH NIH R01** · ROCKEFELLER UNIVERSITY · 2021 · $594,284

## Abstract

Project Summary
There are more than 250 million carriers of chronic hepatitis B virus (HBV) worldwide at risk of developing liver
cirrhosis and hepatocellular carcinoma. To reduce this risk, two anti-HBV therapies are available: nucleoside
analogs and interferon alpha (IFNα). Nucleoside analogs suppress viral replication but rarely lead to a cure
due to the stability of the HBV genome as a covalently closed circular DNA (cccDNA). In contrast, IFNα cures
approximately 10% of patients, but treatment has severe side effects and most patients don't benefit.
Therefore, well-tolerated and more effective treatments are needed.
 Because IFNα can cure HBV, we sought to elucidate which interferon stimulated genes (ISGs) and
pathways inhibit HBV. To this end, we screened a collection of ISGs and identified a potent HBV inhibitor. In
addition, while conducting a genome-wide knockout screen for adenovirus, we identified a cellular protein that
we later found was also necessary for HBV infection. Here we propose to characterize the mechanism of
action of these two host factors and determine which cellular pathways affect HBV infection.
 Many aspects of the HBV lifecycle are not well understood due to the lack of robust in vitro and in vivo
model systems. In recent years we have applied many of our liver systems and our expertise honed while
studying hepatitis C virus to study hepatitis B virus. These efforts have laid the foundation for the proposed
work and the model systems we will use while carrying out this work are a unique strength of the proposal.
Overall, with our proposed work we will gain further insight into HBV biology and the host determinants of HBV
infection. We hope this will uncover new strategies to cure chronic HBV infection.

## Key facts

- **NIH application ID:** 10165482
- **Project number:** 5R01AI143295-03
- **Recipient organization:** ROCKEFELLER UNIVERSITY
- **Principal Investigator:** Charles M Rice
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $594,284
- **Award type:** 5
- **Project period:** 2019-06-10 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10165482

## Citation

> US National Institutes of Health, RePORTER application 10165482, In search of an HBV cure: novel model systems and targets (5R01AI143295-03). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10165482. Licensed CC0.

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