ArticlePLoS pathogens2014
Severe acute respiratory syndrome coronavirus envelope protein ion channel activity promotes virus fitness and pathogenesis.
Article in PLoS pathogens, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 323 papers, 4 of them syntheses that pooled it.
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Who cites it
323 citing papers in PubMed, 4 syntheses or guidelines pooled it, 575 citations in OpenAlex.
- Bibliometric analysis of pyroptosis in pathogenesis and treatment of acute lung injury.Frontiers in medicine · 2024Pooled it
- The Reassessed Potential of SARS-CoV-2 Attenuation for COVID-19 Vaccine Development-A Systematic Review.Viruses · 2022Pooled it
- COVID-19 pandemic: the delta variant, T-cell responses, and the efficacy of developing vaccines.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2022Pooled it
- Review: A systematic review of virus-like particles of coronavirus: Assembly, generation, chimerism and their application in basic research and in the clinic.International journal of biological macromolecules · 2022Pooled it
- Structural insights into an aptainhibitor of the SARS-CoV-2 E protein using molecular docking, molecular dynamics, and biophysical analyses.Molecular therapy. Nucleic acids · 2026Article
- Full-length SARS-CoV-2 envelope protein adopts an interfacial topology in lipid bilayers.Biochimica et biophysica acta. Biomembranes · 2026Article
- Large-scale genomic surveillance reveals immunosuppression drives mutation dynamics in persistent SARS-CoV-2 infections.Nature communications · 2026Article
- Conserved Transmembrane Asparagine Is Essential for the Ion-Conducting Structure and Dynamics of the SARS-CoV-2 Envelope Protein.Journal of the American Chemical Society · 2026Article
- Integrated humoral and inflammatory signatures predict outcomes in severe COVID-19: a 14-day longitudinal analysis.Clinical & translational immunology · 2026Article
- PEDV Structural Proteins with Emphasis on M Protein as an Immunomodulatory Factor in Porcine Innate Immunity.Life (Basel, Switzerland) · 2025Review
- SARS-CoV-2-derived RNA replicons as safe and effective vaccines.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Viroporins: emerging viral infection mechanisms and therapeutic targets.Journal of virology · 2025Review
- Ion channel structure and function of the MERS coronavirus E protein.Science advances · 2025Article
- Human Alveolar Macrophages Detect SARS-CoV-2 Envelope Protein Through TLR2 and TLR4 and Secrete Cytokines in Response.Immunology · 2025Article
- Advances in Viroporin Function and Structure: A Comparative Analysis of Alphavirus 6K with Well-Characterized Viroporins.Viruses · 2025Review
- COVID-19 Seroprevalence in Romania: Insights from a Nationwide Antibody Study.Epidemiologia (Basel, Switzerland) · 2025Article
- Highly versatile small virus-encoded proteins in cellular membranes: A structural perspective on how proteins' inherent conformational plasticity couples with host membranes' properties to control cellular processes.Journal of structural biology: X · 2025Article
- A BSL-2 chimeric system designed to screen SARS-CoV-2 E protein ion channel inhibitors.Journal of virology · 2025Article
- The effect of asparagine-13 in porcine epidemic diarrhea virus envelope protein on pathogenicity.Veterinary research · 2025Article
- Solid-State NMR of Virus Membrane Proteins.Accounts of chemical research · 2025Article
263 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
Deletion of Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) envelope (E) gene attenuates the virus. E gene encodes a small multifunctional protein that possesses ion channel (IC) activity, an important function in virus-host interaction. To test the contribution of E protein IC activity in virus pathogenesis, two recombinant mouse-adapted SARS-CoVs, each containing one single amino acid mutation that suppressed ion conductivity, were engineered. After serial infections, mutant viruses, in general, incorporated compensatory mutations within E gene that rendered active ion channels. Furthermore, IC activity conferred better fitness in competition assays, suggesting that ion conductivity represents an advantage for the virus. Interestingly, mice infected with viruses displaying E protein IC activity, either with the wild-type E protein sequence or with the revertants that restored ion transport, rapidly lost weight and died. In contrast, mice infected with mutants lacking IC activity, which did not incorporate mutations within E gene during the experiment, recovered from disease and most survived. Knocking down E protein IC activity did not significantly affect virus growth in infected mice but decreased edema accumulation, the major determinant of acute respiratory distress syndrome (ARDS) leading to death. Reduced edema correlated with lung epithelia integrity and proper localization of Na+/K+ ATPase, which participates in edema resolution. Levels of inflammasome-activated IL-1β were reduced in the lung airways of the animals infected with viruses lacking E protein IC activity, indicating that E protein IC function is required for inflammasome activation. Reduction of IL-1β was accompanied by diminished amounts of TNF and IL-6 in the absence of E protein ion conductivity. All these key cytokines promote the progression of lung damage and ARDS pathology. In conclusion, E protein IC activity represents a new determinant for SARS-CoV virulence.
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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.