Epigenetic regulation and its therapeutic potential in hepatitis B virus covalently closed circular DNA

Jihua Ren1, Shengtao Cheng1, Fang Ren2

  • 1The Key Laboratory of Molecular Biology of Infectious Diseases Designated by the Chinese Ministry of Education, Chongqing Medical University, Chongqing 400000, China.

Genes & Diseases
|November 13, 2024
PubMed

Insights

Hepatitis B virus (HBV) infection persists due to viral DNA (cccDNA). Understanding cccDNA transcription regulation is key to developing a cure for chronic hepatitis B, offering hope for complete HBV resolution.

Area of Science:

  • Hepatology
  • Virology
  • Molecular Biology

Background:

  • Hepatitis B virus (HBV) infection causes significant liver disease, including cancer.
  • Current therapies suppress HBV replication but rarely achieve complete viral clearance.
  • Persistent covalently closed circular DNA (cccDNA) is the primary barrier to HBV cure.

Purpose of the Study:

  • To review the biology of HBV cccDNA.
  • To summarize mechanisms regulating cccDNA transcription.
  • To discuss novel therapeutic strategies targeting cccDNA for HBV eradication.

Main Methods:

  • Literature review of HBV cccDNA biology and regulation.
  • Analysis of studies on chromatin modifiers, viral proteins, and noncoding RNAs affecting cccDNA.
  • Synthesis of current knowledge on anti-HBV approaches aimed at cccDNA elimination.

Main Results:

  • HBV cccDNA forms stable nuclear minichromosomes.
  • Chromatin-modifying enzymes, viral proteins, and noncoding RNAs critically regulate cccDNA transcription.
  • Understanding these regulatory mechanisms is crucial for developing curative HBV therapies.

Conclusions:

  • Targeting cccDNA transcription represents a promising strategy for a functional cure of chronic hepatitis B.
  • Further research into cccDNA regulatory networks will accelerate the development of novel anti-HBV treatments.
  • Eliminating cccDNA is essential for achieving complete resolution of HBV infection.

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