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Detection of Low Copy Number Integrated Viral DNA Formed by In Vitro Hepatitis B Infection
Published on: November 7, 2018
New Insights on Molecular Mechanism of Hepatitis B Virus Covalently Closed Circular DNA Formation
Alexander L Marchetti1,2, Haitao Guo2,3
1Department of Microbiology and Immunology, School of Medicine, Indiana University, Indianapolis, IN 46202, USA.
Insights
Hepatitis B Virus (HBV) covalently closed circular DNA (cccDNA) persists in patients, causing chronic disease. This review analyzes recent findings on host factors involved in HBV cccDNA formation, a key step toward a cure.
Area of Science:
- Hepatology
- Virology
- Molecular Biology
Background:
- The Hepatitis B Virus (HBV) covalently closed circular DNA (cccDNA) is a stable episomal genome responsible for chronic hepatitis B.
- Eliminating cccDNA is crucial for a functional cure of HBV infection.
- Understanding the formation of cccDNA from relaxed circular DNA (rcDNA) and the host factors involved has been a major research challenge.
Purpose of the Study:
- To review and analyze recent research on the host factors involved in the biosynthesis of HBV cccDNA.
- To elucidate the molecular pathways governing cccDNA formation.
Main Methods:
- Literature review of recent scientific reports.
- Analysis of studies investigating host cellular functions hijacked by HBV.
- Examination of molecular mechanisms underlying cccDNA biosynthesis.
Main Results:
- Recent studies have identified several cellular factors crucial for HBV cccDNA formation.
- Evidence suggests HBV utilizes host DNA repair pathways to convert rcDNA into cccDNA.
- Specific host factors play distinct roles in the molecular pathway of cccDNA biosynthesis.
Conclusions:
- Host cellular factors are integral to the formation of HBV cccDNA.
- Targeting these host factors presents a potential therapeutic strategy for HBV cure.
- Further research into the cccDNA lifecycle is essential for developing effective treatments.
Abstract:
The chronic factor of the Hepatitis B Virus (HBV), specifically the covalently closed circular DNA (cccDNA), is a highly stable and active viral episomal genome established in the livers of chronic hepatitis B patients as a constant source of disease. Being able to target and eliminate cccDNA is the end goal for a genuine cure for HBV. Yet how HBV cccDNA is formed from the viral genomic relaxed circular DNA (rcDNA) and by what host factors had been long-standing research questions. It is generally acknowledged that HBV hijacks cellular functions to turn the open circular DNA conformation of rcDNA into cccDNA through DNA repair mechanisms. With great efforts from the HBV research community, there have been several recent leaps in our understanding of cccDNA formation. It is our goal in this review to analyze the recent reports showing evidence of cellular factor's involvement in the molecular pathway of cccDNA biosynthesis.
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