Dynamics of Hepatitis B Virus Covalently Closed Circular DNA: A Mini-Review

Jie-Li Hu1, Ai-Long Huang1

  • 1Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Chongqing Medical University, Chongqing 400016, China.

Microorganisms
|March 29, 2023
PubMed

Insights

Eradicating hepatitis B virus cccDNA requires understanding its half-life, influenced by host cell turnover and therapy. This review analyzes factors affecting cccDNA decay and proposes strategies for chronic hepatitis B treatment.

Area of Science:

  • Hepatology
  • Virology
  • Molecular Biology

Background:

  • Chronic hepatitis B (CHB) therapy aims to eliminate cccDNA, the viral DNA form persisting in hepatocytes.
  • Understanding cccDNA dynamics, particularly its half-life, is crucial for developing effective CHB treatment strategies.
  • cccDNA half-life is not an intrinsic property but reflects host cell factors and viral clearance mechanisms.

Purpose of the Study:

  • To analyze key factors influencing cccDNA half-life in CHB.
  • To identify research gaps concerning cccDNA decay mechanisms.
  • To explain discrepancies in cccDNA half-life observed during nucleot(s)ide analog (NUC) therapy.

Main Methods:

  • Literature review and analysis of existing data on cccDNA dynamics.
  • Examination of host cell factors, including hepatocyte turnover and noncytopathic effects.
  • Evaluation of NUC therapy's impact on cccDNA pool decline.

Main Results:

  • cccDNA decay is primarily driven by hepatocyte turnover and noncytopathic effects.
  • Observed discrepancies in cccDNA half-life exist between short-term and long-term NUC treatments.
  • Multi-phasic decline patterns of cccDNA during NUC therapy require further investigation.

Conclusions:

  • Hepatocyte lifespan significantly impacts cccDNA half-life, often more than cccDNA intrinsic properties.
  • Further research is needed to elucidate the complex factors governing cccDNA decay.
  • A framework based on cccDNA dynamics can guide the development of novel anti-HBV strategies.

Related Concept Videos

Retrovirus Life Cycles01:10

Retrovirus Life Cycles

Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the retrovirus to...
Size and Structure of Viral Genomes01:26

Size and Structure of Viral Genomes

Viral genomes exhibit remarkable diversity in size, structure, and composition, influencing their replication strategies and interactions with host cells. These genomes consist of either DNA or RNA and may be linear or circular. Additionally, they can be single-stranded or double-stranded, with each configuration affecting how the virus propagates within a host. RNA viruses, for instance, generally have smaller genomes than DNA viruses, a factor that contributes to their high mutation rates and...
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
Subviral Agents01:29

Subviral Agents

Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
Hepatitis01:25

Hepatitis

Hepatitis is an inflammatory condition of the liver most commonly caused by hepatotropic viruses (A–E), though non-infectious causes such as alcohol and drugs also exist.Hepatitis AHepatitis A virus (HAV) is a non-enveloped RNA virus of the Picornaviridae family. It is primarily transmitted via the fecal-oral route, typically through ingestion of contaminated food or water. After ingestion, HAV enters the bloodstream through the oropharynx or intestinal epithelium and reaches the liver. The...
Viral Hepatitis I: Introduction01:28

Viral Hepatitis I: Introduction

Viral hepatitis is an inflammatory condition of the liver caused by infection with hepatotropic viruses, most commonly hepatitis A, B, C, D, and E. Despite variations in structure and transmission, all viruses mentioned infect hepatocytes and provoke immune responses that can hinder liver function. Additionally, some non-hepatotropic viruses can also lead to hepatic inflammation.Hepatitis A VirusHepatitis A virus (HAV) is transmitted through the fecal–oral route, typically by ingestion of food...