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Updated: Aug 18, 2025

Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle
09:35

Development of a Hepatitis B Virus Reporter System to Monitor the Early Stages of the Replication Cycle

Published on: February 1, 2017

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Nonproductive Hepatitis B Virus Covalently Closed Circular DNA Generates HBx-Related Transcripts from the

Bo Peng1,2, Zhiyi Jing2, Zhongmin Zhou2,3

  • 1Graduate program in School of Life Sciences, Peking University, Beijing, China.

Journal of Virology
|December 8, 2022
PubMed

Insights

Hepatitis B virus (HBV) infection persists due to active cccDNA transcription in single liver cells. Superinfection can activate nonproductive transcription, and cccDNA can produce HBx protein to drive further viral gene expression.

Area of Science:

  • Virology
  • Hepatology
  • Molecular Biology

Background:

  • Hepatitis B virus (HBV) infection is a global health concern.
  • Persistent HBV relies on cccDNA transcription in hepatocytes, poorly understood at the single-cell level.
  • Current treatments suppress but rarely cure HBV, highlighting the need for functional cures.

Purpose of the Study:

  • To investigate HBV cccDNA transcription dynamics in single primary human hepatocytes.
  • To characterize viral transcript profiles and their regulation at the single-cell level.
  • To elucidate mechanisms of cccDNA transcription activation and HBx protein's role.

Main Methods:

  • Isolation of primary human hepatocytes from HBV-infected liver-humanized FRG mice.
  • 5' transcriptome sequencing (RNA-seq) to analyze cccDNA transcripts in single cells.
  • Cell infection assays using recombinant HBV to study transcription activation.

Main Results:

  • Single-cell RNA-seq identified distinct HBV transcript profiles, including full transcription or X gene-only transcription.
  • Nonproductive cccDNA transcription can be activated by superinfection with incoming HBV.
  • cccDNA can be transcribed to produce HBx protein, essential for other viral gene transcription.

Conclusions:

  • HBV cccDNA transcription is heterogeneous at the single-cell level.
  • Superinfection and HBx production are key mechanisms in HBV persistence and replication.
  • Findings offer insights for developing strategies to achieve functional cure of chronic HBV infection.

Keywords:
cccDNAhepatitis B virussingle cell sequencetranscription

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