Hepatitis B virus cccDNA: Formation, regulation and therapeutic potential

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Yuchen Xia1, Haitao Guo2

  • 1State Key Laboratory of Virology and Hubei Province Key Laboratory of Allergy and Immunology, School of Basic Medical Sciences, Wuhan University, Wuhan, China.

Antiviral Research
|May 26, 2020
PubMed

Insights

Hepatitis B virus (HBV) infection affects millions globally. This review explores HBV covalently closed circular DNA (cccDNA) formation and regulation, discussing strategies for its eradication to potentially cure chronic HBV.

Area of Science:

  • Hepatology
  • Virology
  • Immunology

Background:

  • Chronic Hepatitis B virus (HBV) infection impacts over 257 million people worldwide.
  • Current antiviral therapies manage HBV replication but do not offer a cure.
  • HBV establishes a persistent cccDNA minichromosome in hepatocytes, a key barrier to eradication.

Purpose of the Study:

  • To review the mechanisms of HBV covalently closed circular DNA (cccDNA) formation.
  • To summarize regulatory pathways controlling cccDNA.
  • To discuss potential therapeutic strategies targeting cccDNA for HBV eradication.

Main Methods:

  • Comprehensive literature review of HBV cccDNA formation and regulation.
  • Analysis of current and emerging therapeutic approaches targeting cccDNA.
  • Synthesis of knowledge on cccDNA persistence and host interactions.

Main Results:

  • Detailed overview of the molecular processes involved in cccDNA establishment and maintenance.
  • Identification of key host factors and viral proteins influencing cccDNA stability.
  • Exploration of diverse strategies, including gene editing and host immune modulation, for cccDNA targeting.

Conclusions:

  • HBV cccDNA represents a critical obstacle to achieving a functional cure for chronic Hepatitis B.
  • Targeting cccDNA formation, maintenance, or clearance is essential for developing curative therapies.
  • Further research into cccDNA biology and innovative therapeutic strategies is crucial for HBV eradication.

Keywords:
Drug targetHBV cccDNA minichromosomeHBV cureHost-virus interactionTranscriptional regulationcccDNA eradication

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