# Regulation of Hepatitis B Virus Capsid Assembly

> **NIH NIH R01** · PENNSYLVANIA STATE UNIV HERSHEY MED CTR · 2020 · $385,755

## Abstract

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. HBV is a small DNA virus and replicates its DNA
genome via reverse transcription of a RNA intermediate called the pregenomic RNA (pgRNA). Viral replication
depends critically on the assembly of a nucleocapsid (NC) that is composed of the viral core or capsids protein
(HBc) and encapsidates a copy each of pgRNA and the reverse transcriptase (RT), which converts the RNA
pregenome to the DNA genome within the NC. Viral capsids also encapsidate the host cyclin-dependent
kinase 2 (CDK2) via unknown mechanisms. Challenging the current dogma that capsid assembly depends
solely on the N-terminal domain (NTD) of HBc, we have recently discovered that under physiological
conditions, capsid assembly critically depends on the C-terminal domain (CTD) of HBc. Furthermore, we have
developed a mammalian cell-free system that recapitulates CTD-dependent capsid assembly and further
regulates capsid assembly through host-mediated CTD phosphorylation and dephosphorylation. The cell-free
capsid assembly system also recapitulates the specific encapsidation of CDK2. Building on these
developments, we propose to dissect the role of CTD, and its state of phosphorylation as regulated by cellular
protein kinases and phosphatases, in capsid assembly (Specific Aim 1). We also plan to elucidate the HBc and
CDK2 requirements for CDK2 encapsidation (Specific Aim 2). Furthermore, we have recently developed
methods to isolate the viral pgRNA in complex with RT, which is the substrate recognized by HBc during NC
assembly to achieve specific encapsidation of pgRNA and RT. We now propose to combine the isolation of the
pgRNA-RT complex together with the cell-free capsid assembly system to develop cell-free systems for the
specific packaging of pgRNA (and RT) into NCs (Specific Aim 3).

## Key facts

- **NIH application ID:** 9988151
- **Project number:** 5R01AI127670-05
- **Recipient organization:** PENNSYLVANIA STATE UNIV HERSHEY MED CTR
- **Principal Investigator:** Jianming Hu
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $385,755
- **Award type:** 5
- **Project period:** 2016-09-23 → 2021-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9988151

## Citation

> US National Institutes of Health, RePORTER application 9988151, Regulation of Hepatitis B Virus Capsid Assembly (5R01AI127670-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9988151. Licensed CC0.

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