Related Experiment Video

Updated: Jun 25, 2025

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target
11:34

A Competent Hepatocyte Model Examining Hepatitis B Virus Entry through Sodium Taurocholate Cotransporting Polypeptide as a Therapeutic Target

Published on: May 10, 2022

2.2K

Roles Played by DOCK11, a Guanine Nucleotide Exchange Factor, in HBV Entry and Persistence in Hepatocytes

Ying-Yi Li1, Kazuhisa Murai2, Junyan Lyu2

  • 1Department of Gastroenterology, Kanazawa University Graduate School of Medicine, 13-1, Takaramachi, Kanazawa 920-8640, Japan.

Viruses
|May 25, 2024
PubMed

Insights

Dedicator of cytokinesis 11 (DOCK11) protein aids Hepatitis B virus (HBV) persistence by enabling viral DNA transcription and replication. Inhibiting DOCK11 with 10M-D42AN suppresses HBV, offering a potential therapeutic strategy for chronic hepatitis B.

Area of Science:

  • Hepatology
  • Virology
  • Molecular Biology

Background:

  • Hepatitis B virus (HBV) infection persistence is linked to viral covalently closed circular DNA (cccDNA).
  • Dedicator of cytokinesis 11 (DOCK11), a guanine nucleotide exchange factor (GEF) for CDC42, is implicated in HBV persistence.

Purpose of the Study:

  • To elucidate the role of DOCK11 in HBV replication and persistence.
  • To investigate DOCK11's interaction with viral components and host cellular machinery.
  • To evaluate DOCK11 inhibition as a therapeutic strategy for chronic hepatitis B (CHB).

Main Methods:

  • Immunofluorescence and co-immunoprecipitation to study DOCK11 localization and interactions.
  • Analysis of HBV replication and cccDNA transcription in the presence and absence of DOCK11.
  • In vitro and in vivo studies using the DOCK11-binding peptide 10M-D42AN and entecavir.

Main Results:

  • DOCK11 facilitates an alternative retrograde trafficking route for HBV from early endosomes to the trans-Golgi network and endoplasmic reticulum, evading lysosomal degradation.
  • DOCK11 promotes HBV cccDNA transcription by associating it with H3K4me3 and RNA Polymerase II.
  • DOCK11 is essential for cccDNA synthesis, and its inhibition by 10M-D42AN suppresses HBV replication.
  • Combined treatment with 10M-D42AN and entecavir showed promising results in suppressing HBV.

Conclusions:

  • DOCK11 is a critical host factor for HBV persistence, involved in viral trafficking, cccDNA transcription, and replication.
  • Targeting DOCK11 with inhibitors like 10M-D42AN represents a potential therapeutic avenue for CHB.
  • DOCK11 is a promising candidate molecule for developing targeted therapies against CHB.

Keywords:
DOCK11cccDNA persistencehepatitis B virusretrograde trafficking

More Related Videos

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System05:55

Identifying Inhibitors of the HBx-DDB1 Interaction Using a Split Luciferase Assay System

Published on: December 21, 2019

6.7K
Modeling Hepatitis B Virus Infection in Non-Hepatic 293T-NE-3NRs Cells09:02

Modeling Hepatitis B Virus Infection in Non-Hepatic 293T-NE-3NRs Cells

Published on: June 5, 2020

7.4K

Related Concept Videos

Coat Assembly and GTPases01:33

Coat Assembly and GTPases

Vesicles incorporate different coat protein subunits in different cell locations, which changes the properties of the coat, such as the shape and geometry of the transport vesicles. Thus, vesicle coat proteins also play a significant role in cargo selection.
Coat assembly depends on the local availability of phosphatidylinositol phosphates or PIPs and GTP-binding proteins. Adaptor proteins, which link the coat proteins to the membrane, bind to these PIPs and play a crucial role in controlling...
3.5K
Rab Proteins01:14

Rab Proteins

Rab proteins constitute the largest family of monomeric GTPases, of which 70 members are present in humans. Rab proteins and their effectors regulate consecutive stages of vesicle transport such as vesicle transport, docking, and fusion to the correct recipient membrane.
Rab proteins switch between a cytosolic, GDP-bound inactive state and a membrane-anchored, GTP-bound active state. By themselves, Rabs show slow rates of GDP/GTP exchange and GTP hydrolysis. Thus, Rab proteins are considered...
3.9K
Regulation of Nuclear Protein Sorting01:45

Regulation of Nuclear Protein Sorting

Nuclear protein sorting regulates nucleus composition and gene expression, crucial for determining the fate of a eukaryotic cell. Hence, the entry and exit of molecules across the nuclear envelope is a tightly controlled process. Nuclear protein sorting can be inhibited by one of the following ways: 1) masking cargo signal sequences, 2) modifying the nuclear receptor's affinity for cargo, 3) controlling the nuclear pore size, 4) retaining the cargo during its transit to the cytosol or the...
2.4K
GPI Anchoring of Proteins in the ER Membrane01:29

GPI Anchoring of Proteins in the ER Membrane

GPI-anchoring is a post-translational, reversible protein modification that is ubiquitous in eukaryotes. Such proteins are primarily present on the exoplasmic leaflet of the plasma membrane.
GPI-anchor structure
A sequence of 11 enzymatic reactions results in the synthesis of the complete GPI anchor consisting of a hydrophobic and a hydrophilic portion. The hydrophobic portion comprises phosphatidylinositol, while the hydrophilic part comprises polar groups like phosphoethanolamine,...
4.0K
Pinching-off of Coated Vesicles01:32

Pinching-off of Coated Vesicles

Vesicle budding is orchestrated by distinct cytosolic proteins such as adaptor proteins, coat proteins, and GTPases. To initiate vesicle budding, membrane-bending proteins containing crescent-shaped BAR domains bind to the lipid heads in the bilayer and distort the membrane to form a protein-coated vesicle bud. Adaptors proteins such as AP2 for clathrin-coated vesicles can nucleate on the deformed membrane. Finally, coat proteins such as clathrin or COPI and COPII assemble into a coat forming...
3.1K
Tail-anchoring of Proteins in the ER Membrane01:45

Tail-anchoring of Proteins in the ER Membrane

Tail-anchored, or TA, proteins are estimated to make up to 3-5% of membrane proteins found in the eukaryotic cell. Such proteins have a single transmembrane domain located approximately 30 amino acid residues upstream from the C-terminal end. As a result, the signal recognition particle (SRP) cannot guide a TA protein to the ER membrane for cotranslational insertion. Hence, they are integrated into the ER membrane post-translationally using their C-terminal end as the anchor. TA proteins...
3.1K