ArticlePLoS pathogens2022
Hypoxia inducible factors regulate infectious SARS-CoV-2, epithelial damage and respiratory symptoms in a hamster COVID-19 model.
Article in PLoS pathogens, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 26 citations in OpenAlex.
- Identification of HIF1A as a therapeutic target during SARS-CoV-2-associated lung injury.JCI insight · 2025Trial
- Hypoxia Inducible Factor 1α-dependent Induction of Alveolar miR-147b Dampens SARS-CoV-2-associated Acute Respiratory Distress Syndrome via Direct Targeting of Viral RNA.Anesthesiology · 2026Article
- Hypoxia inducible factors regulate pneumovirus replication by enhancing innate immune sensing.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Hypoxia: a critical pathophysiological driver in respiratory inflammatory diseases.Military Medical Research · 2026Review
- Airway immunometabolic responses during pulmonary bacterial and viral infections.Cell reports · 2025Review
- Article
- Hypoxia increases susceptibility of human intestinal epithelial cells to rotavirus infection through repression of interferon induction.Gut microbes · 2025Article
- Role of Hypoxia-Inducible Factors in Respiratory Syncytial Virus Infection-Associated Lung Disease.International journal of molecular sciences · 2025Article
- Hypoxia-inducible-factors differentially contribute to clinical disease and viral replication during RSV infection.bioRxiv : the preprint server for biology · 2024Article
- Ciclopirox inhibits SARS-CoV-2 replication by promoting the degradation of the nucleocapsid protein.Acta pharmaceutica Sinica. B · 2024Article
- Targeting hypoxia-inducible factors: therapeutic opportunities and challenges.Nature reviews. Drug discovery · 2024Review
- The HIF transcription network exerts innate antiviral activity in neurons and limits brain inflammation.Cell reports · 2024Article
- Hypoxia inducible factors inhibit respiratory syncytial virus infection by modulation of nucleolin expression.iScience · 2024Article
- CCR5/CXCR3 antagonist TAK-779 prevents diffuse alveolar damage of the lung in the murine model of the acute respiratory distress syndrome.Frontiers in pharmacology · 2024Article
- The N6-methyladenosine demethylase ALKBH5 regulates the hypoxic HBV transcriptome.PLoS pathogens · 2024Article
- Mechanism of COVID-19-Induced Cardiac Damage from Patient, In Vitro and Animal Studies.Current heart failure reports · 2023Review
- Why Is Iron Deficiency/Anemia Linked to Alzheimer's Disease and Its Comorbidities, and How Is It Prevented?Biomedicines · 2023Review
- Hypoxia dampens innate immune signalling at early time points and increases Zika virus RNA levels in iPSC-derived macrophages.The Journal of general virology · 2023Article
- Targeting 2-Oxoglutarate-Dependent Dioxygenases Promotes Metabolic Reprogramming That Protects against Lethal SARS-CoV-2 Infection in the K18-hACE2 Transgenic Mouse Model.ImmunoHorizons · 2023Article
- An ACAT inhibitor suppresses SARS-CoV-2 replication and boosts antiviral T cell activity.PLoS pathogens · 2023Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 2 countries.
Funding
Abstract
Understanding the host pathways that define susceptibility to Severe-acute-respiratory-syndrome-coronavirus-2 (SARS-CoV-2) infection and disease are essential for the design of new therapies. Oxygen levels in the microenvironment define the transcriptional landscape, however the influence of hypoxia on virus replication and disease in animal models is not well understood. In this study, we identify a role for the hypoxic inducible factor (HIF) signalling axis to inhibit SARS-CoV-2 infection, epithelial damage and respiratory symptoms in the Syrian hamster model. Pharmacological activation of HIF with the prolyl-hydroxylase inhibitor FG-4592 significantly reduced infectious virus in the upper and lower respiratory tract. Nasal and lung epithelia showed a reduction in SARS-CoV-2 RNA and nucleocapsid expression in treated animals. Transcriptomic and pathological analysis showed reduced epithelial damage and increased expression of ciliated cells. Our study provides new insights on the intrinsic antiviral properties of the HIF signalling pathway in SARS-CoV-2 replication that may be applicable to other respiratory pathogens and identifies new therapeutic opportunities.
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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.