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Updated: Oct 15, 2025

Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection

Published on: November 7, 2018

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Regulatory function of interferon-inducible 44-like for hepatitis B virus covalently closed circular DNA in primary

Takuto Nosaka1, Tatsushi Naito1, Yosuke Murata1

  • 1Second Department of Internal Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan.

Hepatology Research : the Official Journal of the Japan Society of Hepatology
|October 26, 2021
PubMed

Insights

Researchers identified Interferon-induced protein 44-like (IFI44L) as a key host factor regulating hepatitis B virus (HBV) covalently closed circular DNA (cccDNA). This discovery offers a new molecular strategy for controlling HBV infection by targeting IFI44L.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Hepatitis B virus (HBV) infection cure necessitates eliminating covalently closed circular DNA (cccDNA).
  • Interferon (IFN)-γ shows antiviral potential but cannot eliminate cccDNA.
  • Enhancing regulatory effects requires understanding host factors and IFN actions.

Purpose of the Study:

  • To comprehensively analyze host factors linked to cccDNA amplification.
  • To investigate the effects of IFN-γ and IFN-α on HBV transcription.
  • To identify novel molecular targets for HBV cccDNA regulation.

Main Methods:

  • Utilized an in vitro HBV infection system with primary human hepatocytes.
  • Employed genomic plasmids with specific HBV mutations (A1762T/G1764A, G1896A).
  • Conducted microarray and small interfering RNA analyses to identify host factors.

Main Results:

  • Established an HBV infection model reflecting various propagation levels.
  • Identified 53 genes correlated with cccDNA levels via microarray analysis.
  • Discovered Interferon-induced protein 44-like (IFI44L) upregulation by IFN-γ/α, inhibiting NF-κB and STAT1 pathways.

Conclusions:

  • Identified IFI44L as an IFN-inducible molecule associated with cccDNA amplification in vitro.
  • IFI44L demonstrates anti-HBV effects by modulating key signaling pathways.
  • Suggests IFI44L as a novel molecular target for regulating HBV cccDNA.
Abstract

Keywords:
covalently closed circular DNAhepatitis B virusinterferoninterferon-induced protein 44-likeprimary human hepatocyte

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