ArticleJournal of hepatology2021
Hypoxia inducible factors regulate hepatitis B virus replication by activating the basal core promoter.
Article in Journal of hepatology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Hypoxia increases the activity of oncolytic adenoviruses through HIF-2α-stimulated E1A expression.Signal transduction and targeted therapy · 2026Article
- Glutamine-Linked Cellular Stress Responses in Viral Infection: Mechanisms, Crosstalk, and Future Perspectives.International journal of molecular sciences · 2026Review
- Identification of Cyclin L1 as a Host Factor Regulating Hepatitis B Virus Replication.Viruses · 2026Article
- Article
- Spatial transcriptomics and single-nucleus RNA sequencing reveal rAAV2- and rAAV9-specific transduction signatures in the mouse liver.Gene therapy · 2026Article
- Mechanisms and Management Strategies of Hepatocarcinogenesis Driven by Chronic Hepatitis B Comorbid with Type 2 Diabetes.Microorganisms · 2026Review
- Spatial transcriptional profiling of CHB liver biopsies reveals an undetected population of zonally biased HBV-integrated cells.JHEP reports : innovation in hepatology · 2026Article
- CHB-Induced Immune Zonation Chaos Elicited LXRα-mediated Lipid Metabolism Disorders in Kupffer Cells to Induce Cancer Stem Cell Formation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role of Integrated HBV DNA in the Quest for a Cure in HIV/HBV co-infection.Current HIV/AIDS reports · 2025Review
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- Differential profiles of autophagy and Nrf2-mediated antioxidant response in HBeAg-positive versus HBeAg-negative chronic hepatitis B patients.Frontiers in microbiology · 2025Article
- Hypoxic reactivation of Kaposi's sarcoma associated herpesvirus.Cell insight · 2024Review
- Hepatitis B virus enhancer 1 activates preS1 and preS2 promoters of integrated HBV DNA impairing HBsAg secretion.JHEP reports : innovation in hepatology · 2024Article
- Harnessing CD8Clinical and translational medicine · 2024Review
- 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
- A bibliometric analysis of m6A methylation in viral infection from 2000 to 2022.Virology journal · 2024Article
- The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome.PLoS pathogens · 2024Article
- A small molecule iCDM-34 identified by in silico screening suppresses HBV DNA through activation of aryl hydrocarbon receptor.Cell death discovery · 2023Article
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Authors and funding
23 authors at 8 institutions in 5 countries.
Funding
Abstract
BACKGROUND &
aimsHypoxia inducible factors (HIFs) are a hallmark of inflammation and are key regulators of hepatic immunity and metabolism, yet their role in HBV replication is poorly defined. HBV replicates in hepatocytes within the liver, a naturally hypoxic organ, however most studies of viral replication are performed under conditions of atmospheric oxygen, where HIFs are inactive. We therefore investigated the role of HIFs in regulating HBV replication.
methodsUsing cell culture, animal models, human tissue and pharmacological agents inhibiting the HIF-prolyl hydroxylases, we investigated the impact of hypoxia on the HBV life cycle.
resultsCulturing liver cell-based model systems under low oxygen uncovered a new role for HIFs in binding HBV DNA and activating the basal core promoter, leading to increased pre-genomic RNA and de novo HBV particle secretion. The presence of hypoxia responsive elements among all primate members of the hepadnaviridae highlights an evolutionary conserved role for HIFs in regulating this virus family.
conclusionsIdentifying a role for this conserved oxygen sensor in regulating HBV transcription suggests that this virus has evolved to exploit the HIF signaling pathway to persist in the low oxygen environment of the liver. Our studies show the importance of considering oxygen availability when studying HBV-host interactions and provide innovative routes to better understand and target chronic HBV infection. LAY SUMMARY: Viral replication in host cells is defined by the cellular microenvironment and one key factor is local oxygen tension. Hepatitis B virus (HBV) replicates in the liver, a naturally hypoxic organ. Hypoxia inducible factors (HIFs) are the major sensors of low oxygen; herein, we identify a new role for these factors in regulating HBV replication, revealing new therapeutic targets.
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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.