Related Experiment Video
Updated: Jun 17, 2026
05:55
Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System
Published on: December 21, 2019
DOCK11 promotes HBV cccDNA formation through a PARP1-dependent mechanism.
Hideo Takayama1, Kouki Nio1, Kazuyuki Kuroki1
1Department of Gastroenterology, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan.
Microbiology Spectrum
|June 16, 2026
Summary
Dedicator of cytokinesis 11 (DOCK11) promotes Hepatitis B virus (HBV) persistence by aiding the formation of viral cccDNA. Targeting DOCK11 may offer new therapies to reduce cccDNA and cure chronic HBV infection.
Area of Science:
- Hepatology and Virology
- Molecular Biology and Biochemistry
Background:
- Hepatitis B virus (HBV) infection persists due to stable cccDNA in hepatocytes, driving chronic liver disease and cancer.
- Current antiviral therapies are ineffective against HBV cccDNA, necessitating research into its formation and maintenance.
- Poly(ADP-ribose) polymerase 1 (PARP1) is implicated in converting HBV rcDNA to cccDNA.
Purpose of the Study:
- To elucidate the role of dedicator of cytokinesis 11 (DOCK11) in HBV cccDNA formation and maintenance.
- To investigate the molecular mechanisms underlying DOCK11's involvement in cccDNA synthesis.
- To assess DOCK11 as a potential therapeutic target for chronic HBV infection.
Main Methods:
- Utilized a minicircle HBV cccDNA reporter assay in DOCK11-depleted hepatoma cells.
- Performed cell-free assays with HBV rcDNA and nuclear extracts to assess DOCK11's effect on cccDNA formation.
- Employed co-immunoprecipitation and liquid chromatography-mass spectrometry to identify interacting proteins.
- Assessed PARP1 recruitment to DNA damage sites and its association with rcDNA in DOCK11 knockout cells.
Main Results:
- DOCK11 depletion significantly impaired HBV cccDNA maintenance and formation.
- DOCK11 overexpression enhanced cccDNA formation, while DOCK11 knockout suppressed it in cell-free assays.
- DOCK11 was found to form a multiprotein complex with HBV DNA, including PARP1.
- DOCK11 knockout reduced PARP1 recruitment to rcDNA, suggesting a role in facilitating PARP1 association.
Conclusions:
- DOCK11 promotes HBV cccDNA formation, likely by facilitating the recruitment and function of PARP1.
- DOCK11 represents a novel host factor crucial for HBV persistence.
- Targeting the DOCK11-PARP1 interaction offers a potential therapeutic strategy for eliminating HBV cccDNA and achieving a functional cure.
Related Concept Videos
01:25Hepatitis
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...
01:51Mechanisms of Retrovirus-induced Cancers
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
01:51Mechanisms of Retrovirus-induced Cancers
Retroviruses are RNA viruses that have been shown to cause cancers in diverse species, including chickens, mice, cats, and monkeys. The RNA genomes of these viruses are first reverse-transcribed into single and then double-stranded DNA (dsDNA) copies. This dsDNA called proviral DNA then integrates into the host genome. Subsequently, the host cell transcribes the proviral DNA in concert with the chromosomal DNA. This leads to the production of viral RNA and proteins that assemble at the host...
01:02Long-patch Base Excision Repair
Since the discovery of the two BER pathways, there has been a debate about how a cell chooses one pathway over the other and the factors determining this selection. Numerous in vitro experiments have pointed out multiple determinants for the sub-pathway selection. These are:
02:37Restarting Stalled Replication Forks
DNA replication is initiated at sites containing predefined DNA sequences known as origins of replication. DNA is unwound at these sites by the minichromosome maintenance (MCM) helicase and other factors such as Cdc45 and the associated GINS complex.The unwound single strands are protected by replication protein A (RPA) until DNA polymerase starts synthesizing DNA at the 5’ end of the strand in the same direction as the replication fork. To prevent the replication fork from falling apart, a...
01:29Viruses 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...