ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2009
Influenza virus M2 protein inhibits epithelial sodium channels by increasing reactive oxygen species.
Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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Who cites it
53 citing papers in PubMed, 94 citations in OpenAlex.
- Targeting virus-interacting host ion channels as a novel antiviral strategy.Acta pharmacologica Sinica · 2026Review
- Connexin-hemichannels-mediated ATP release causes lung injury following chlorine inhalation.American journal of physiology. Cell physiology · 2025Article
- Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins.Viruses · 2025Review
- The long road to Ithaca: a physiologist's journey.American journal of physiology. Cell physiology · 2025Review
- The pathogenesis of influenza in intact alveoli: virion endocytosis and its effects on the lung's air-blood barrier.Frontiers in immunology · 2024Review
- Vitisin B inhibits influenza A virus replication by multi-targeting neuraminidase and virus-induced oxidative stress.Acta pharmaceutica Sinica. B · 2023Article
- COVID-19 and Liquid Homeostasis in the Lung-A Perspective through the Epithelial Sodium Channel (ENaC) Lens.Cells · 2022Review
- Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.Frontiers in immunology · 2022Review
- Unravelling the Immunomodulatory Effects of Viral Ion Channels, towards the Treatment of Disease.Viruses · 2021Review
- Dysregulation of ion transport in the lung epithelium infected with SARS-CoV-2.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- SARS-CoV-2 may hijack GPCR signaling pathways to dysregulate lung ion and fluid transport.American journal of physiology. Lung cellular and molecular physiology · 2021Article
- Metabolic host response and therapeutic approaches to influenza infection.Cellular & molecular biology letters · 2020Review
- Respiratory Barrier as a Safeguard and Regulator of Defense Against Influenza A Virus andFrontiers in immunology · 2020Review
- Influenza A Virus Infection Induces Apical Redistribution of NaAmerican journal of respiratory cell and molecular biology · 2019Article
- Influenza M2 protein regulates MAVS-mediated signaling pathway through interacting with MAVS and increasing ROS production.Autophagy · 2019Article
- Viroporins in the Influenza Virus.Cells · 2019Review
- Coronavirus envelope protein: current knowledge.Virology journal · 2019Review
- Loss of barrier integrity in alveolar epithelial cells downregulates ENaC expression and activity via CaPflugers Archiv : European journal of physiology · 2018Article
- Influenza-mediated reduction of lung epithelial ion channel activity leads to dysregulated pulmonary fluid homeostasis.JCI insight · 2018Article
- The role of respiratory epithelium in host defence against influenza virus infection.Biomedical journal · 2018Review
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
The mechanisms by which replicating influenza viruses decrease the expression and function of amiloride-sensitive epithelial sodium channels (ENaCs) have not been elucidated. We show that expression of M2, a transmembrane influenza protein, decreases ENaC membrane levels and amiloride-sensitive currents in both Xenopus oocytes, injected with human alpha-, beta-, and gamma-ENaCs, and human airway cells (H441 and A549), which express native ENaCs. Deletion of a 10-aa region within the M2 C terminus prevented 70% of this effect. The M2 ENaC down-regulation occurred at normal pH and was prevented by MG-132, a proteasome and lysosome inhibitor. M2 had no effect on Liddle ENaCs, which have decreased affinity for Nedd4-2. H441 and A549 cells transfected with M2 showed higher levels of reactive oxygen species, as shown by the activation of redox-sensitive dyes. Pretreatment with glutathione ester, which increases intracellular reduced thiol concentrations, or protein kinase C (PKC) inhibitors prevented the deleterious effects of M2 on ENaCs. The data suggest that M2 protein increases steady-state concentrations of reactive oxygen intermediates that simulate PKC and decrease ENaCs by enhancing endocytosis and its subsequent destruction by the proteasome. These novel findings suggest a mechanism for the influenza-induced rhinorrhea and life-threatening alveolar edema in humans.
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Registered trials
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