ArticleHepatology (Baltimore, Md.)2021
Hypoxia-Inducible Factor 1 Alpha-Mediated RelB/APOBEC3B Down-regulation Allows Hepatitis B Virus Persistence.
Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 32 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Article
- The central regulator HIF-1α in digestive system pathologies: inflammation and cancer.Frontiers in immunology · 2026Review
- NF-κB is a central regulator of hypoxia-induced gene expression.EMBO reports · 2026Article
- The Role of Integrated HBV DNA in the Quest for a Cure in HIV/HBV co-infection.Current HIV/AIDS reports · 2025Review
- Chronic Hepatitis B: Current Management and Future Directions.Diseases (Basel, Switzerland) · 2025Review
- Hepatitis B virus confers innate immunity evasion through hepatitis B virus-miR-3 down-regulation of cGAS-Sting-IFN signaling.World journal of hepatology · 2025Article
- Oxidative Stress Enhances Rubella Virus Infection in Immortalized Human First-Trimester Trophoblasts.International journal of molecular sciences · 2025Article
- Classification and regulatory interactions of key transcription factors in COVID-19.Frontiers in cellular and infection microbiology · 2025Review
- HBV-miR-3 and cGAS-STING axis: a new frontier in hepatitis B therapy.Frontiers in cellular and infection microbiology · 2025Article
- HIV coinfection exacerbates HBV-induced liver fibrogenesis through a HIF-1α- and TGF-β1-dependent pathway.Journal of hepatology · 2024Article
- Oxygen-dependent histone lysine demethylase 4 restricts hepatitis B virus replication.The Journal of biological chemistry · 2024Article
- p-STAT3-elevated E3 ubiquitin ligase DTX4 confers the stability of HBV cccDNA by ubiquitinating APOBEC3B in liver.Theranostics · 2024Article
- The Mechanism of APOBEC3B in Hepatitis B Virus Infection and HBV Related Hepatocellular Carcinoma Progression, Therapeutic and Prognostic Potential.Infection and drug resistance · 2024Review
- The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome.PLoS pathogens · 2024Article
- The scientific basis of combination therapy for chronic hepatitis B functional cure.Nature reviews. Gastroenterology & hepatology · 2023Review
- Article
- Generation and Utilization of a Monoclonal Antibody against Hepatitis B Virus Core Protein for a Comprehensive Interactome Analysis.Microorganisms · 2022Article
- Identification of Estradiol Benzoate as an Inhibitor of HBx Using Inducible Stably Transfected HepG2 Cells Expressing HiBiT Tagged HBx.Molecules (Basel, Switzerland) · 2022Article
- Hypoxia signaling in human health and diseases: implications and prospects for therapeutics.Signal transduction and targeted therapy · 2022Review
Corrections and comments
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Authors and funding
25 authors at 7 institutions in 5 countries.
Funding
Abstract
BACKGROUND AND
aimsTherapeutic strategies against HBV focus, among others, on the activation of the immune system to enable the infected host to eliminate HBV. Hypoxia-inducible factor 1 alpha (HIF1α) stabilization has been associated with impaired immune responses. HBV pathogenesis triggers chronic hepatitis-related scaring, leading inter alia to modulation of liver oxygenation and transient immune activation, both factors playing a role in HIF1α stabilization. APPROACH AND
resultsWe addressed whether HIF1α interferes with immune-mediated induction of the cytidine deaminase, apolipoprotein B mRNA editing enzyme catalytic subunit 3B (APOBEC3B; A3B), and subsequent covalently closed circular DNA (cccDNA) decay. Liver biopsies of chronic HBV (CHB) patients were analyzed by immunohistochemistry and in situ hybridization. The effect of HIF1α induction/stabilization on differentiated HepaRG or mice ± HBV ± LTβR-agonist (BS1) was assessed in vitro and in vivo. Induction of A3B and subsequent effects were analyzed by RT-qPCR, immunoblotting, chromatin immunoprecipitation, immunocytochemistry, and mass spectrometry. Analyzing CHB highlighted that areas with high HIF1α levels and low A3B expression correlated with high HBcAg, potentially representing a reservoir for HBV survival in immune-active patients. In vitro, HIF1α stabilization strongly impaired A3B expression and anti-HBV effect. Interestingly, HIF1α knockdown was sufficient to rescue the inhibition of A3B up-regulation and -mediated antiviral effects, whereas HIF2α knockdown had no effect. HIF1α stabilization decreased the level of v-rel reticuloendotheliosis viral oncogene homolog B protein, but not its mRNA, which was confirmed in vivo. Noteworthy, this function of HIF1α was independent of its partner, aryl hydrocarbon receptor nuclear translocator.
conclusionsIn conclusion, inhibiting HIF1α expression or stabilization represents an anti-HBV strategy in the context of immune-mediated A3B induction. High HIF1α, mediated by hypoxia or inflammation, offers a reservoir for HBV survival in vivo and should be considered as a restricting factor in the development of immune therapies.
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