ArticlePloS one2009
The SARS Coronavirus 3a protein causes endoplasmic reticulum stress and induces ligand-independent downregulation of the type 1 interferon receptor.
Article in PloS one, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 171 papers, 2 of them syntheses that pooled it.
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Who cites it
171 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- [Pulmonary innate immune response in Sars-cov-2 infection]Revista de la Facultad de Ciencias Medicas (Cordoba, Argentina) · 2022Pooled it
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- Trial
- Endoplasmic reticulum stress and the unfolded protein response in lung diseases: molecular pathways and therapeutic interventions.The Journal of pathology · 2026Review
- Coronavirus M protein disperses the trans-Golgi network and inhibits anterograde protein trafficking in the secretory pathway.PLoS pathogens · 2026Article
- MERS-CoV and SARS-CoV-1 proteins inhibit the IFN-α JAK/STAT pathway of epithelial cells, via IFN-λ-induced USP18.Frontiers in immunology · 2026Article
- Immune-Boosting and Antiviral Effects of Antioxidants in COVID-19 Pneumonia: A Therapeutic Perspective.Life (Basel, Switzerland) · 2025Review
- Porcine epidemic diarrhea virus E protein induces unfolded protein response through activating both PERK and ATF6 rather than IRE1 signaling pathway.Virus genes · 2024Article
- A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation.Journal of biomedical science · 2024Review
- Characterization of humoral immune responses against SARS-CoV-2 accessory proteins in infected patients and mouse model.Virologica Sinica · 2024Article
- Regulatory Non-Coding RNAs during Porcine Viral Infections: Potential Targets for Antiviral Therapy.Viruses · 2024Review
- Expression of SARS-CoV-2 Nonstructural Proteins 3 and 4 Can Tune the Unfolded Protein Response in Cell Culture.Journal of proteome research · 2024Article
- A comprehensive SARS-CoV-2 and COVID-19 review, Part 2: host extracellular to systemic effects of SARS-CoV-2 infection.European journal of human genetics : EJHG · 2024Review
- Article
- Pathophysiological involvement of host mitochondria in SARS-CoV-2 infection that causes COVID-19: a comprehensive evidential insight.Molecular and cellular biochemistry · 2023Review
- Article
- Possible Pathogenesis and Prevention of Long COVID: SARS-CoV-2-Induced Mitochondrial Disorder.International journal of molecular sciences · 2023Review
- SARS-CoV-2 Harnesses Host Translational Shutoff and Autophagy To Optimize Virus Yields: the Role of the Envelope (E) Protein.Microbiology spectrum · 2023Article
- Contribution to pathogenesis of accessory proteins of deadly human coronaviruses.Frontiers in cellular and infection microbiology · 2023Review
- SARS-CoV-2PeerJ · 2023Article
111 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV) is reported to cause apoptosis of infected cells and several of its proteins including the 3a accessory protein, are pro-apoptotic. Since the 3a protein localizes to the endoplasmic reticulum (ER)-Golgi compartment, its role in causing ER stress was investigated in transiently transfected cells. Cells expressing the 3a proteins showed ER stress based on activation of genes for the ER chaperones GRP78 and GRP94. Since ER stress can cause differential modulation of the unfolded protein response (UPR), which includes the inositol-requiring enzyme 1 (IRE-1), activating transcription factor 6 (ATF6) and PKR-like ER kinase (PERK) pathways, these were individually tested in 3a-expressing cells. Only the PERK pathway was found to be activated in 3a-expressing cells based on (1) increased phosphorylation of eukaryotic initiation factor 2 alpha (eIF2alpha) and inhibitory effects of a dominant-negative form of eIF2alpha on GRP78 promoter activity, (2) increased translation of activating transcription factor 4 (ATF4) mRNA, and (3) ATF4-dependent activation of the C/EBP homologous protein (CHOP) gene promoter. Activation of PERK affects innate immunity by suppression of type 1 interferon (IFN) signaling. The 3a protein was found to induce serine phosphorylation within the IFN alpha-receptor subunit 1 (IFNAR1) degradation motif and to increase IFNAR1 ubiquitination. Confocal microscopic analysis showed increased translocation of IFNAR1 into the lysosomal compartment and flow cytometry showed reduced levels of IFNAR1 in 3a-expressing cells. These results provide further mechanistic details of the pro-apoptotic effects of the SARS-CoV 3a protein, and suggest a potential role for it in attenuating interferon responses and innate immunity.
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Registered trials
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