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Hepatitis B Virus cccDNA Formation
- Molecular classification
- Viral DNA, DNA replication process
01
Overview
Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) formation is the process by which relaxed circular DNA (rcDNA) is converted into cccDNA in the nucleus of infected hepatocytes. cccDNA serves as the transcriptional template for all HBV RNAs, including pregenomic RNA (pgRNA), and is essential for viral persistence and replication. The conversion of rcDNA into cccDNA involves removal of viral polymerase, terminal redundancy sequences, and RNA primers, completion of plus-strand DNA synthesis, and ligation. Host cell DNA repair machinery, including FEN1, TDP2, and POLK, are hijacked for this process. cccDNA forms a minichromosome structure that regulates gene expression. Targeting cccDNA formation is a key therapeutic strategy for achieving functional cure of chronic hepatitis B.
02
Mechanism of action
Inhibition of cccDNA formation or promotion of cccDNA degradation
03
Biological functions
Viral replicationTranscriptionGenome maintenance
04
Disease associations
Hepatitis BChronic Hepatitis BCirrhosisHepatocellular carcinoma
05
Safety considerations
Viral resistanceOff-target effects on host DNA repairIncomplete cccDNA elimination leading to relapse
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