ArticleSignal transduction and targeted therapy2021
HIF-1α promotes SARS-CoV-2 infection and aggravates inflammatory responses to COVID-19.
Article in Signal transduction and targeted therapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 182 papers, 1 of them a synthesis that pooled it.
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Who cites it
182 citing papers in PubMed, 1 synthesis or guideline pooled it, 252 citations in OpenAlex.
- Roles of hypoxia inducible factors in viral infection: Are they a potential therapeutic target?Virulence · 2025Pooled it
- Adhatoda vasica and Tinospora cordifolia extracts ameliorate clinical and molecular markers in mild COVID-19 patients: a randomized open-label three-armed study.European journal of medical research · 2023Trial
- HSV-1 metabolic hijacking: Mechanisms to precision therapeutics.Virulence · 2026Review
- Multiple Sclerosis and Viruses: « Liaisons Dangereuses ».Reviews in medical virology · 2026Review
- The accessory protein ORF3a hijacks the CLCC1 chloride channel to disrupt ER homeostasis in betacoronavirus pathogenesis.Cell discovery · 2026Article
- Comparative proteomics of human naso-oropharyngeal swabs from COVID19 patients for identification of potential biomarker candidates.Biochemistry and biophysics reports · 2026Article
- ZDHHC18-Mediated Palmitoylation of ORF3a Promotes SARS-CoV-2 Pathogenesis by Antagonizing TRIM16-Mediated Ubiquitination and Proteasomal Degradation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The HIF-1α-Th17/Treg axis in pediatric infectious mononucleosis: a clinical investigation of metabolic-immune dysregulation.BMC infectious diseases · 2026Article
- Mitochondrial OXPHOS restricts SARS-CoV-2 replication.Science advances · 2026Article
- Host metabolic responses to SARS-CoV-2 and influenza viruses: parallels and contrasts.Metabolomics : Official journal of the Metabolomic Society · 2026Review
- PTBP1 is upregulated in response to Zika virus infection and restrains viral replication by hijacking viral NS1 protein to induce NS1 degradation.Journal of virology · 2026Article
- Potential causal role of mitochondrial biological effects in COVID-19: Evidence from Mendelian randomization study.Medicine · 2026Article
- When Viruses Talk through Extracellular Vesicles: a New Perspective on Sars-Cov-2-Induced Neurodegeneration.Journal of extracellular vesicles · 2026Article
- Sexual dimorphism of COVID-19 inspires drug repositioning and host-targeting immunotherapy for viral pneumonia.Signal transduction and targeted therapy · 2026Article
- Stage-specific regulation of KSHV infection by HIF-1α.Journal of virology · 2026Article
- The neuro-vascular-immune triad: the interactive network in the tumor microenvironment.Cell communication and signaling : CCS · 2026Review
- Human Influenza Virus Infection: A Focus on Key Host Determinants Linked to Clinical Disease Severity.Viruses · 2026Review
- Advances in the Research of Hypoxia-Inducible Factor-1Alpha and Plasminogen Activator Inhibitor-1 in Vascular-Related Diseases.Journal of clinical medicine research · 2026Review
- Chronic hypoxia adaptation at high altitude: a perspective on Its potential role in mortality in viral pneumonia-associated ARDS and implications for personalized critical care.Critical care (London, England) · 2026Review
- Digoxin attenuates LPS-induced acute lung injury in mice via NF-κB and HIF-1α inhibition.Biomolecules & biomedicine · 2026Article
122 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 5 institutions in 1 country.
Funding
Abstract
Cytokine storm induced by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a major pathological feature of Coronavirus Disease 2019 (COVID-19) and a crucial determinant in COVID-19 prognosis. Understanding the mechanism underlying the SARS-CoV-2-induced cytokine storm is critical for COVID-19 control. Here, we identify that SARS-CoV-2 ORF3a and host hypoxia-inducible factor-1α (HIF-1α) play key roles in the virus infection and pro-inflammatory responses. RNA sequencing shows that HIF-1α signaling, immune response, and metabolism pathways are dysregulated in COVID-19 patients. Clinical analyses indicate that HIF-1α production, inflammatory responses, and high mortalities occurr in elderly patients. HIF-1α and pro-inflammatory cytokines are elicited in patients and infected cells. Interestingly, SARS-CoV-2 ORF3a induces mitochondrial damage and Mito-ROS production to promote HIF-1α expression, which subsequently facilitates SARS-CoV-2 infection and cytokines production. Notably, HIF-1α also broadly promotes the infection of other viruses. Collectively, during SARS-CoV-2 infection, ORF3a induces HIF-1α, which in turn aggravates viral infection and inflammatory responses. Therefore, HIF-1α plays an important role in promoting SARS-CoV-2 infection and inducing pro-inflammatory responses to COVID-19.
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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.