ArticleCellular and molecular gastroenterology and hepatology2023
Hepatitis B Virus Utilizes a Retrograde Trafficking Route via the Trans-Golgi Network to Avoid Lysosomal Degradation.
Article in Cellular and molecular gastroenterology and hepatology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 11 citations in OpenAlex.
- Structural basis for membrane-dependent positive feedback regulation of DOCK11 by activated Cdc42.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Review
- Chromatin Accessibility-Guided Targeting Identifies Structurally Constrained Regions in HBV cccDNA and Suppresses Viral Replication.International journal of molecular sciences · 2026Article
- DOCK11 promotes HBV cccDNA formation through a PARP1-dependent mechanism.Microbiology spectrum · 2026Article
- Meta-analysis of functional genomics studies reveals conserved cellular pathways required by viruses of pandemic concern.Access microbiology · 2026Article
- Netrin-1 inhibits the attachment and internalization of Hepatitis B virus for hepatocyte infection.PLoS pathogens · 2025Article
- Wnt/β-Catenin Signaling Regulates Hepatitis B Virus cccDNA Levels.International journal of molecular sciences · 2025Article
- Hepatitis B virus entry, assembly, and egress.Microbiology and molecular biology reviews : MMBR · 2024Review
- SPG21, a potential oncogene targeted by miR-128-3p, amplifies HBx-induced carcinogenesis and chemoresistance via activation of TRPM7-mediated JNK pathway in hepatocellular carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Lipid nanoparticle-encapsulated DOCK11-siRNA efficiently reduces hepatitis B virus cccDNA level in infected mice.Molecular therapy. Methods & clinical development · 2024Article
- Article
- Roles Played by DOCK11, a Guanine Nucleotide Exchange Factor, in HBV Entry and Persistence in Hepatocytes.Viruses · 2024Review
- Prevalence, characteristics, and virologic correlations of hepatitis delta (D) among patients with hepatitis B surface antigen in Mongolia.Global health & medicine · 2024Article
- Nanocomplexes of doxorubicin and DNA fragments for efficient and safe cancer chemotherapy.Journal of controlled release : official journal of the Controlled Release Society · 2023Article
- Back to the Roots: Noncanonical Retrograde Trafficking of the HBV Nucleocapsids.Cellular and molecular gastroenterology and hepatology · 2023Article
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Authors and funding
27 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsHepatitis B virus (HBV) infection is difficult to cure owing to the persistence of covalently closed circular viral DNA (cccDNA). We performed single-cell transcriptome analysis of newly established HBV-positive and HBV-negative hepatocellular carcinoma cell lines and found that dedicator of cytokinesis 11 (DOCK11) was crucially involved in HBV persistence. However, the roles of DOCK11 in the HBV lifecycle have not been clarified.
methodsThe cccDNA levels were measured by Southern blotting and real-time detection polymerase chain reaction in various hepatocytes including PXB cells by using an HBV-infected model. The retrograde trafficking route of HBV capsid was investigated by super-resolution microscopy, proximity ligation assay, and time-lapse analysis. The downstream molecules of DOCK11 and underlying mechanism were examined by liquid chromatography-tandem mass spectrometry, immunoblotting, and enzyme-linked immunosorbent assay.
resultsThe cccDNA levels were strongly increased by DOCK11 overexpression and repressed by DOCK11 suppression. Interestingly, DOCK11 functionally associated with retrograde trafficking proteins in the trans-Golgi network (TGN), Arf-GAP with GTPase domain, ankyrin repeat, and pleckstrin homology domain-containing protein 2 (AGAP2), and ADP-ribosylation factor 1 (ARF1), together with HBV capsid, to open an alternative retrograde trafficking route for HBV from early endosomes (EEs) to the TGN and then to the endoplasmic reticulum (ER), thereby avoiding lysosomal degradation. Clinically, DOCK11 levels in liver biopsies from patients with chronic hepatitis B were significantly reduced by entecavir treatment, and this reduction correlated with HBV surface antigen levels.
conclusionsHBV uses a retrograde trafficking route via EEs-TGN-ER for infection that is facilitated by DOCK11 and serves to maintain cccDNA. Therefore, DOCK11 is a potential therapeutic target to prevent persistent HBV infection.
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