ArticleNature2016
Hepatitis B virus X protein identifies the Smc5/6 complex as a host restriction factor.
Article in Nature, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 336 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
336 citing papers in PubMed, 528 citations in OpenAlex.
- Farnesoid X receptor agonist for the treatment of chronic hepatitis B: A safety study.Journal of viral hepatitis · 2021Trial
- Combining antiviral therapy with cancer treatment in HBV-associated HCC: A translational approach.Virus research · 2026Review
- Human cytomegalovirus antagonizes SMC5/6 driven genome silencing via UL35 instituted proteasomal degradation of SLF2.PLoS pathogens · 2026Article
- Structural basis of diverse substrate recruitment by the HIV-1 Vpr-hijacked CRL4(VprBP) E3 ligase.PLoS pathogens · 2026Article
- [The E3 ubiquitin ligase KLHL8 degrades HBx protein via the ubiquitin-proteasome pathway and inhibits HBV cccDNA transcription].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- The PTM switches of HBx: Master regulators of HBV infection and liver oncogenesis.Virus research · 2026Review
- HBx Enhances the Nrf2/ARE-dependent Antioxidant Response by Promoting Nuclear Export and Downregulation of Bach1.The Kobe journal of medical sciences · 2026Article
- The Multifunctional SMC5/6 Complex in Genome Stability, Antiviral Restriction, and Human Disease.Current issues in molecular biology · 2026Review
- Structural and functional insights into HBx-Smc6 targeting for HBV inhibition.Cell research · 2026Article
- Article
- Synthesis of Nitazoxanide Derivatives as Potent and Orally Available HBx-DDB1 Inhibitors against Hepatitis B Virus.ACS medicinal chemistry letters · 2026Article
- Review
- CDW19S coordinates phasic end processing via distinct enzymatic activities.Nucleic acids research · 2026Article
- HBx-Associated Reactivation of the IGF2 Locus in Chronic HBV Infection and HBV-Related Hepatocarcinogenesis: Evidence Boundaries and Biomarker Implications.Biomedicines · 2026Review
- Generation of HBV cccDNA using single-stranded M13 phage DNA for authentic minichromosome functionality.Journal of virology · 2026Article
- HBV HBx protein masks epigenetic reader Spindlin1 via an inter-molecular zinc finger to subvert transcriptional control.Nature communications · 2026Article
- Hepatitis B virus-induced hepatocellular carcinoma: HBx-associated epigenetic mechanisms and therapeutic opportunities.Cancer gene therapy · 2026Review
- Combination therapy with tobevibart and elebsiran potently reduces hepatitis B virus surface antigen levels in preclinicalAntimicrobial agents and chemotherapy · 2026Article
- hnRNPA2B1 induces HBV cccDNA degradation by recruiting APOBEC3B.Nucleic acids research · 2026Article
- Chromatin remodeler BAF maintains HBV cccDNA transcriptional competence and represents a therapeutic target.Nucleic acids research · 2026Article
276 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic hepatitis B virus infection is a leading cause of cirrhosis and liver cancer. Hepatitis B virus encodes the regulatory HBx protein whose primary role is to promote transcription of the viral genome, which persists as an extrachromosomal DNA circle in infected cells. HBx accomplishes this task by an unusual mechanism, enhancing transcription only from extrachromosomal DNA templates. Here we show that HBx achieves this by hijacking the cellular DDB1-containing E3 ubiquitin ligase to target the 'structural maintenance of chromosomes' (Smc) complex Smc5/6 for degradation. Blocking this event inhibits the stimulatory effect of HBx both on extrachromosomal reporter genes and on hepatitis B virus transcription. Conversely, silencing the Smc5/6 complex enhances extrachromosomal reporter gene transcription in the absence of HBx, restores replication of an HBx-deficient hepatitis B virus, and rescues wild-type hepatitis B virus in a DDB1-knockdown background. The Smc5/6 complex associates with extrachromosomal reporters and the hepatitis B virus genome, suggesting a direct mechanism of transcriptional inhibition. These results uncover a novel role for the Smc5/6 complex as a restriction factor selectively blocking extrachromosomal DNA transcription. By destroying this complex, HBx relieves the inhibition to allow productive hepatitis B virus gene expression.
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Registered trials
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.