# Hepatitis B virus e antigen in viral persistence

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2021 · $412,500

## Abstract

Hepatitis B virus (HBV) can cause severe liver diseases including cirrhosis and hepatocellular carcinoma
(HCC). There are approximately 350 million people in the world that are chronically infected by this virus,
resulting in 0.5-1 million deaths every year. Most chronic HBV carriers acquired the virus early in life from their
infected mothers through vertical transmission. In contrast, patients who acquired HBV from other adults through
horizontal transmission will usually develop self-limited acute infection. Why vertical transmission leads to
chronic infection whereas horizontal transmission leads to self-limited acute infection is unclear. HBV has a very
narrow host range, which has greatly hampered its research. We have recently developed a mouse model to
study the maternal effect on HBV persistence in the offspring. By crossing female hemizygous HBV transgenic
mice to male naïve mice, we obtained non-transgenic mouse pups. When these non-transgenic mouse pups
were injected with the HBV genomic DNA by hydrodynamic injection, the HBV replication persisted in the mouse
liver for up to seven months. This is in contrast to control mice born to non-transgenic mothers, which cleared
HBV after 3-4 weeks of HBV DNA injection. Our further studies indicated that the maternal HBV e antigen
(HBeAg) could condition the Kupffer cells of the offspring, which would undergo M2 polarization to support HBV
persistence upon re-stimulation by HBeAg. The goal of this application is to continue these previous studies to
further investigate how HBeAg interacts with Kupffer cells. Specifically, we will determine how HBeAg stimulates
Kupffer cells and to identify the putative HBeAg receptor in these cells. We will also determine whether HBeAg
by itself is sufficient to condition Kupffer cells of the offspring to support HBV persistence and whether Kupffer
cells by themselves are sufficient to support HBV persistence. We will also test the hypothesis that HBeAg
conditions Kupffer cells in utero to suppress the immune response to HBV in the offspring. Finally, we will study
the HBV basal core promoter mutant, which has reduced expression of HBeAg and is associated with chronic
hepatitis and an increased risk for HCC, to test whether this reduction of HBeAg expression leads to the partial
loss of immune tolerance. The proposed studies will provide important information for us to understand the
mechanism of HBV persistence after vertical transmission and to improve the treatments for chronic HBV
patients.

## Key facts

- **NIH application ID:** 10159091
- **Project number:** 5R01AI129540-05
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** J.-H. James Ou
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $412,500
- **Award type:** 5
- **Project period:** 2017-06-20 → 2023-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10159091

## Citation

> US National Institutes of Health, RePORTER application 10159091, Hepatitis B virus e antigen in viral persistence (5R01AI129540-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10159091. Licensed CC0.

---

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