# Mechanisms of Hepadnavirus Assembly and Replication

> **NIH NIH R37** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2024 · $483,339

## Abstract

Hepatitis B virus (HBV) is a major cause of chronic viral hepatitis that increases dramatically the risk of liver
cancer and other end-stage liver diseases such as cirrhosis. The major obstacle to curing chronic HBV
infection is the persistence of the viral nuclear episome, the covalently closed circular (CCC) DNA, which is
derived from the relaxed circular (RC) DNA contained within the viral nucleocapsid. Moreover, the inability
of mouse hepatocytes to support CCC DNA formation remains a major hurdle in the development of an
immuno-competent mouse model for HBV infection. This MERIT Award Extension application builds on,
and extends, our current work on the disassembly of viral nucleocapsids (uncoating), which releases the
RC DNA into the host cell nucleus, a prerequisite step for nuclear CCC DNA formation but also exposing
RC DNA for potential degradation or triggering of host cell DNA sensing and immune responses. The main
goal of the Extension is to better understand viral and host control of HBV CCC DNA formation and
infection. Four Specific Aims are proposed. Aim 1 will elucidate the deficiencies in mouse hepatocytes for
HBV infection. Aim 2 will develop cell-free systems for nucleocapsid uncoating and CCC DNA formation.
Aim 3 will define the late HBV entry events controlled by the viral capsid and host factors. Aim 4 will assess
the role of DNA sensing in HBV infection.
RELEVANCE (See instructions):
The hepatitis B virus (HBV) is a global cause of chronic liver diseases, including liver cirrhosis and cancer.
We propose to elucidate the mechanisms of, and viral and host factors involved in, the viral trafficking
events during infection and the disassembly of HBV nucleocapsid, which are essential but poorly
understood steps in viral replication and contribute to the host tropism of HBV. These studies will bring
novel insights into HBV infection and nucleocapsid disassembly and facilitate ongoing efforts to develop
novel antiviral agents targeted at these processes as well as mouse models of HBV infection.

## Key facts

- **NIH application ID:** 10869921
- **Project number:** 5R37AI043453-27
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Jianming Hu
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $483,339
- **Award type:** 5
- **Project period:** 1999-02-15 → 2028-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10869921

## Citation

> US National Institutes of Health, RePORTER application 10869921, Mechanisms of Hepadnavirus Assembly and Replication (5R37AI043453-27). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10869921. Licensed CC0.

---

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