ArticleJournal of virology2019
Spatiotemporal Analysis of Hepatitis B Virus X Protein in Primary Human Hepatocytes.
Article in Journal of virology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- The PTM switches of HBx: Master regulators of HBV infection and liver oncogenesis.Virus research · 2026Review
- HBV HBx protein masks epigenetic reader Spindlin1 via an inter-molecular zinc finger to subvert transcriptional control.Nature communications · 2026Article
- The Intrinsic Innate Immunity of Hepatocytes Suppresses HBV Replication and Is Antagonized by HBx.Viruses · 2025Article
- Sequential backbone chemical shift assignments of a cancer-associated isoform of the HBx protein from human hepatitis B virus.Biomolecular NMR assignments · 2025Article
- Targeting HBV with RNA interference: Paths to cure.Science translational medicine · 2025Review
- Structural basis of the hepatitis B virus X protein in complex with DDB1.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Article
- The Intrinsically Disordered Region of HBx and Virus-Host Interactions: Uncovering New Therapeutic Approaches for HBV and Cancer.International journal of molecular sciences · 2025Review
- Evaluation of the role of unconventional prefoldin RPB5 interactor (URI1) in hepatitis B virus infection.Virology journal · 2025Article
- Modeling metabolic-associated steatohepatitis with human pluripotent stem cell-derived liver organoids.Hepatology communications · 2024Article
- Review
- SMC5/6-Mediated Transcriptional Regulation of Hepatitis B Virus and Its Therapeutic Potential.Viruses · 2024Review
- SMC5/6-Mediated Transcriptional Regulation of Hepatitis B Virus and Its Therapeutic Potential.Viruses · 2024Review
- The impact of HBx protein on mitochondrial dynamics and associated signaling pathways strongly depends on the hepatitis B virus genotype.Journal of virology · 2024Article
- Mechanisms of Hepatitis B Virus cccDNA and Minichromosome Formation and HBV Gene Transcription.Viruses · 2024Review
- Pre- and Post-Transcriptional Control of HBV Gene Expression: The Road Traveled towards the New Paradigm of HBx, Its Isoforms, and Their Diverse Functions.Biomedicines · 2023Review
- Mitochondrial Glycerol-3-Phosphate Dehydrogenase Restricts HBV Replication via the TRIM28-Mediated Degradation of HBx.Journal of virology · 2023Article
- Nonproductive Hepatitis B Virus Covalently Closed Circular DNA Generates HBx-Related Transcripts from the HBx/Enhancer I Region and Acquires Reactivation by Superinfection in Single Cells.Journal of virology · 2023Article
- Antiviral Compounds Screening Targeting HBx Protein of the Hepatitis B Virus.International journal of molecular sciences · 2022Article
- The FirstMicroorganisms · 2022Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The structural maintenance of chromosomes 5/6 complex (Smc5/6) is a host restriction factor that suppresses hepatitis B virus (HBV) transcription. HBV counters this restriction by expressing the X protein (HBx), which redirects the host DNA damage-binding protein 1 (DDB1) E3 ubiquitin ligase to target Smc5/6 for degradation. HBx is an attractive therapeutic target for the treatment of chronic hepatitis B (CHB), but it is challenging to study this important viral protein in the context of natural infection due to the lack of a highly specific and sensitive HBx antibody. In this study, we developed a novel monoclonal antibody that enables detection of HBx protein in HBV-infected primary human hepatocytes (PHH) by Western blotting and immunofluorescence. Confocal imaging studies with this antibody demonstrated that HBx is predominantly located in the nucleus of HBV-infected PHH, where it exhibits a diffuse staining pattern. In contrast, a DDB1-binding-deficient HBx mutant was detected in both the cytoplasm and nucleus, suggesting that the DDB1 interaction plays an important role in the nuclear localization of HBx. Our study also revealed that HBx is expressed early after infection and has a short half-life (∼3 h) in HBV-infected PHH. In addition, we found that treatment with small interfering RNAs (siRNAs) that target DDB1 or HBx mRNA decreased HBx protein levels and led to the reappearance of Smc6 in the nuclei of HBV-infected PHH. Collectively, these studies provide the first spatiotemporal analysis of HBx in a natural infection system and also suggest that HBV transcriptional silencing by Smc5/6 can be restored by therapeutic targeting of HBx.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.