ArticleBiochimica et biophysica acta2014
The ORF4a protein of human coronavirus 229E functions as a viroporin that regulates viral production.
Article in Biochimica et biophysica acta, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 77 citations in OpenAlex.
- Human Coronavirus 229E Uses ORF4/4a to Antagonize the Host Restriction Factor SERINC5.MedComm · 2026Article
- Human alphacoronavirus replication and innate immune induction in airway culture systems.mBio · 2026Article
- Current Status and Challenges of Vaccine Development for Seasonal Human Coronaviruses.Vaccines · 2025Review
- Changes in ORF4 of HCoV-229E under different culture conditions.The Journal of general virology · 2025Article
- Spike-Independent Infection of Human Coronavirus 229E in Bat Cells.Microbiology spectrum · 2023Article
- Coronavirus accessory protein ORF3 biology and its contribution to viral behavior and pathogenesis.iScience · 2023Review
- SARS-COV-2 viroporins activate the NLRP3-inflammasome by the mitochondrial permeability transition pore.Frontiers in immunology · 2023Article
- Functions of Viroporins in the Viral Life Cycle and Their Regulation of Host Cell Responses.Frontiers in immunology · 2022Review
- SARS-COV-2, infection, transmission, transcription, translation, proteins, and treatment: A review.International journal of biological macromolecules · 2021Review
- Regulation of epithelial sodium channel activity by SARS-CoV-1 and SARS-CoV-2 proteins.Biophysical journal · 2021Article
- Cryo-EM structure of SARS-CoV-2 ORF3a in lipid nanodiscs.Nature structural & molecular biology · 2021Article
- Review
- SARS-CoV-2, the pandemic coronavirus: Molecular and structural insights.Journal of basic microbiology · 2021Review
- The SARS-Coronavirus Infection Cycle: A Survey of Viral Membrane Proteins, Their Functional Interactions and Pathogenesis.International journal of molecular sciences · 2021Review
- Cryo-EM structure of the SARS-CoV-2 3a ion channel in lipid nanodiscs.bioRxiv : the preprint server for biology · 2021Article
- Middle East Respiratory Syndrome Coronavirus Gene 5 Modulates Pathogenesis in Mice.Journal of virology · 2021Article
- Unification and extensive diversification of M/Orf3-related ion channel proteins in coronaviruses and other nidoviruses.Virus evolution · 2021Article
- Potential approaches to combat COVID-19: a mini-review.Molecular biology reports · 2020Review
- UV-LED disinfection of Coronavirus: Wavelength effect.Journal of photochemistry and photobiology. B, Biology · 2020Article
- A rational roadmap for SARS-CoV-2/COVID-19 pharmacotherapeutic research and development: IUPHAR Review 29.British journal of pharmacology · 2020Review
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
In addition to a set of canonical genes, coronaviruses encode additional accessory proteins. A locus located between the spike and envelope genes is conserved in all coronaviruses and contains a complete or truncated open reading frame (ORF). Previously, we demonstrated that this locus, which contains the gene for accessory protein 3a from severe acute respiratory syndrome coronavirus (SARS-CoV), encodes a protein that forms ion channels and regulates virus release. In the current study, we explored whether the ORF4a protein of HCoV-229E has similar functions. Our findings revealed that the ORF4a proteins were expressed in infected cells and localized at the endoplasmic reticulum/Golgi intermediate compartment (ERGIC). The ORF4a proteins formed homo-oligomers through disulfide bridges and possessed ion channel activity in both Xenopus oocytes and yeast. Based on the measurement of conductance to different monovalent cations, the ORF4a was suggested to form a non-selective channel for monovalent cations, although Li(+) partially reduced the inward current. Furthermore, viral production decreased when the ORF4a protein expression was suppressed by siRNA in infected cells. Collectively, this evidence indicates that the HCoV-229E ORF4a protein is functionally analogous to the SARS-CoV 3a protein, which also acts as a viroporin that regulates virus production. This article is part of a Special Issue entitled: Viral Membrane Proteins - Channels for Cellular Networking.
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