ArticleFree radical biology & medicine2015
Respiratory syncytial virus infection down-regulates antioxidant enzyme expression by triggering deacetylation-proteasomal degradation of Nrf2.
Article in Free radical biology & medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed, 85 citations in OpenAlex.
- Nuclear factor erythroid 2-related factor: potential use as a therapeutic strategy for viral infections.Archives of microbiology · 2026Review
- Therapeutic potential of nutritional aryl hydrocarbon receptor ligands for respiratory syncytial virus infection: a mini review.Frontiers in microbiology · 2026Review
- The Dual Role of Nrf2 Signaling in Virus Infections: Antiviral Guardian or Proviral Accomplice?Pathogens (Basel, Switzerland) · 2025Review
- NRF2 agonists 4-octyl-itaconate and dimethyl fumarate reduce human and bovine RSV proliferation and RSV disease in a murine model.ImmunoHorizons · 2025Article
- Flavonoids from Polygonum hydropiper L. regulate PCV2-induced oxidative stress of RAW264.7 cells via Pi3k/AKT and Nrf2/HO-1 signaling pathways.Scientific reports · 2025Article
- Porcine reproductive and respiratory syndrome virus nsp5 inhibits the activation of the Nrf2/HO-1 pathway by targeting p62 to antagonize its antiviral activity.Journal of virology · 2025Article
- Advances in development of antiviral strategies against respiratory syncytial virus.Acta pharmaceutica Sinica. B · 2025Review
- The Role of the Nrf2 Pathway in Airway Tissue Damage Due to Viral Respiratory Infections.International journal of molecular sciences · 2024Review
- Respiratory Virus-Induced PARP1 Alters DC Metabolism and Antiviral Immunity Inducing Pulmonary Immunopathology.Viruses · 2024Article
- Beta-Hydroxybutyrate Mitigates Sensorimotor and Cognitive Impairments in a Photothrombosis-Induced Ischemic Stroke in Mice.International journal of molecular sciences · 2024Article
- Review
- The Role of the NRF2 Pathway in the Pathogenesis of Viral Respiratory Infections.Pathogens (Basel, Switzerland) · 2023Review
- A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer.Cell communication and signaling : CCS · 2023Review
- Dysregulation of intracellular redox homeostasis by the SARS-CoV-2 ORF6 protein.Virology journal · 2023Article
- Oxidative stress and ROS-mediated cellular events in RSV infection: potential protective roles of antioxidants.Virology journal · 2023Review
- Roles of Oxidative Stress and Nrf2 Signaling in Pathogenic and Non-Pathogenic Cells: A Possible General Mechanism of Resistance to Therapy.Antioxidants (Basel, Switzerland) · 2023Review
- SARS-CoV-2 Inhibits NRF2-Mediated Antioxidant Responses in Airway Epithelial Cells and in the Lung of a Murine Model of Infection.Microbiology spectrum · 2023Article
- NRF2 Antioxidant Response and Interferon-Stimulated Genes Are Differentially Expressed in Respiratory-Syncytial-Virus- and Rhinovirus-Infected Hospitalized Children.Pathogens (Basel, Switzerland) · 2023Article
- NRF2 Regulates Cystathionine Gamma-Lyase Expression and Activity in Primary Airway Epithelial Cells Infected with Respiratory Syncytial Virus.Antioxidants (Basel, Switzerland) · 2022Article
- Hydrogen Sulfide Donor GYY4137 Rescues NRF2 Activation in Respiratory Syncytial Virus Infection.Antioxidants (Basel, Switzerland) · 2022Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Respiratory syncytial virus (RSV) is the most important cause of viral acute respiratory tract infections and hospitalizations in children, for which no vaccine or treatment is available. RSV infection in cells, mice, and children leads to rapid generation of reactive oxygen species, which are associated with oxidative stress and lung damage, due to a significant decrease in the expression of airway antioxidant enzymes (AOEs). Oxidative stress plays an important role in the pathogenesis of RSV-induced lung disease, as antioxidants ameliorate clinical disease and inflammation in vivo. The aim of this study is to investigate the unknown mechanism(s) of virus-induced inhibition of AOE expression. RSV infection is shown to induce a progressive reduction in nuclear and total cellular levels of the transcription factor NF-E2-related factor 2 (Nrf2), resulting in decreased binding to endogenous AOE gene promoters and decreased AOE expression. RSV induces Nrf2 deacetylation and degradation via the proteasome pathway in vitro and in vivo. Histone deacetylase and proteasome inhibitors block Nrf2 degradation and increase Nrf2 binding to AOE endogenous promoters, resulting in increased AOE expression. Known inducers of Nrf2 are able to increase Nrf2 activation and subsequent AOE expression during RSV infection in vitro and in vivo, with significant amelioration of oxidative stress. This is the first study to investigate the mechanism(s) of virus-induced inhibition of AOE expression. RSV-induced inhibition of Nrf2 activation, due to deacetylation and proteasomal degradation, could be targeted for therapeutic intervention aimed to increase airway antioxidant capacity during infection.
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