ArticleAutophagy2016
Hepatitis B virus-triggered autophagy targets TNFRSF10B/death receptor 5 for degradation to limit TNFSF10/TRAIL response.
Article in Autophagy, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers, 1 of them a synthesis that pooled it.
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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
45 citing papers in PubMed, 1 synthesis or guideline pooled it, 73 citations in OpenAlex.
- Interplay between Cellular Autophagy and Hepatitis B Virus Replication: A Systematic Review.Cells · 2020Pooled it
- TNFSF10 drives hyperactive immune responses via NLRP3 inflammasome and endoplasmic reticulum stress in autoimmune and inflammatory diseases.Journal of advanced research · 2026Article
- Cytotoxic activity and safety characterization of IMV-M™, a MUC16 × DR5 bispecific antibody.Antibody therapeutics · 2026Article
- Hepatitis B Virus X Protein Upregulates SREBP2 to Modulate Autophagy in Hepatocellular Carcinoma.Cancer medicine · 2025Article
- DR5 is a restriction factor for human herpesviruses.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Endoplasmic reticulum stress regulates apoptosis and chemotherapeutic via enhancing TNFRSF10B recycling to the cell membrane in triple-negative breast cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Article
- PD-1 induces autophagy via the PI3K/AKT/FoxO1 pathway to promote infectious bursal disease virus replication.Frontiers in immunology · 2025Article
- Disease progression associated cytokines in COVID-19 patients with deteriorating and recovering health conditions.Scientific reports · 2024Article
- The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates.Exploration of targeted anti-tumor therapy · 2024Review
- Shared diagnostic genes and potential mechanisms between COVID-19 and sepsis revealed by bioinformatics analysis.World journal of emergency medicine · 2024Article
- Virus-Host Protein Interaction Network of the Hepatitis E Virus ORF2-4 by Mammalian Two-Hybrid Assays.Viruses · 2023Article
- Regulation of host gene expression by J paramyxovirus.PloS one · 2023Article
- SARS-CoV-2 Exploits Non-Canonical Autophagic Processes to Replicate, Mature, and Egress the Infected Vero E6 Cells.Pathogens (Basel, Switzerland) · 2022Article
- Paraoxonase-2 contributes to promoting lipid metabolism and mitochondrial function via autophagy activation.Scientific reports · 2022Article
- Death Receptor DR5 as a Proviral Factor for Viral Entry and Replication of Coronavirus PEDV.Viruses · 2022Article
- Decoding the spatial chromatin organization and dynamic epigenetic landscapes of macrophage cells during differentiation and immune activation.Nature communications · 2022Article
- High expression of H2A histone family member Y promotes the proliferation and autophagy of hepatocellular carcinoma cells.Bioengineered · 2022Article
- Novel Molecular Therapeutics Targeting Signaling Pathway to Control Hepatitis B Viral Infection.Frontiers in cellular and infection microbiology · 2022Review
- Genetic Variations of ALDH (rs671) Are Associated With the Persistence of HBV Infection Among the Chinese Han Population.Frontiers in medicine · 2022Article
- An integrative bioinformatics analysis for identifying hub genes associated with infection of lung samples in patients infected with SARS-CoV-2.European journal of medical research · 2021Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Death receptors of TNFSF10/TRAIL (tumor necrosis factor superfamily member 10) contribute to immune surveillance against virus-infected or transformed cells by promoting apoptosis. Many viruses evade antiviral immunity by modulating TNFSF10 receptor signaling, leading to persistent infection. Here, we report that hepatitis B virus (HBV) X protein (HBx) restricts TNFSF10 receptor signaling via macroautophagy/autophagy-mediated degradation of TNFRSF10B/DR5, a TNFSF10 death receptor, and thus permits survival of virus-infected cells. We demonstrate that the expression of the TNFRSF10B protein is dramatically reduced both in liver tissues of chronic hepatitis B patients and in cell lines transfected with HBV or HBx. HBx-mediated downregulation of TNFRSF10B is caused by the lysosomal, but not proteasomal, degradation pathway. Immunoblotting analysis of LC3B and SQSTM1, and microscopy analysis of tandem-fluorescence-tagged LC3B revealed that HBx promotes complete autophagy. Inhibition of autophagy with a pharmacological inhibitor and LC3B knockdown revealed that HBx-induced autophagy is crucial for TNFRSF10B degradation. Immunoprecipitation and GST affinity isolation assays showed that HBx directly interacts with TNFRSF10B and recruits it to phagophores, the precursors to autophagosomes. We confirmed that autophagy activation is related to the downregulation of the TNFRSF10B protein in liver tissues of chronic hepatitis B patients. Inhibition of autophagy enhanced the susceptibility of HBx-infected hepatocytes to TNFSF10. These results identify the dual function of HBx in TNFRSF10B degradation: HBx plays a role as an autophagy receptor-like molecule, which promotes the association of TNFRSF10B with LC3B; HBx is also an autophagy inducer. Our data suggest a molecular mechanism for HBV evasion from TNFSF10-mediated antiviral immunity, which may contribute to chronic HBV infection.
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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.