ArticleVirus research2021
The ORF8 protein of SARS-CoV-2 induced endoplasmic reticulum stress and mediated immune evasion by antagonizing production of interferon beta.
Article in Virus research, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.
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Who cites it
82 citing papers in PubMed, 124 citations in OpenAlex.
- SARS-CoV-2 ORF8 Exploits Host miRNA Networks to Rewire Post-Transcriptional Regulation.International journal of molecular sciences · 2026Article
- Modulation of Host Innate Immune Response by Highly Pathogenic Human Coronaviruses during Viral Infection.Journal of microbiology and biotechnology · 2026Review
- Redundant and distinct mechanisms suppress innate immune activation during SARS-CoV-2 infection.PLoS biology · 2026Article
- Article
- SARS-CoV-2 ORF8: an accessory protein at the interface of immune evasion and inflammation.Frontiers in immunology · 2026Review
- Pattern Recognition Receptors (PRRs) Expression and Activation in COVID-19 and Long COVID: From SARS-CoV-2 Escape Mechanisms to Emerging PRR-Targeted Immunotherapies.Microorganisms · 2025Review
- Article
- Characteristics and mechanisms of liver injury caused by emerging infectious diseases.Frontiers in immunology · 2025Review
- Strategies Used by SARS-CoV-2 to Evade the Innate Immune System in an Evolutionary Perspective.Pathogens (Basel, Switzerland) · 2024Review
- A portrait of the infected cell: how SARS-CoV-2 infection reshapes cellular processes and pathways.Npj viruses · 2024Review
- SARS-CoV-2 NSP6 reduces autophagosome size and affects viral replication via sigma-1 receptor.Journal of virology · 2024Article
- Viral imitation is the sincerest form of epigenetic flattery.Molecular biology of the cell · 2024Review
- A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation.Journal of biomedical science · 2024Review
- IRE1α recognizes a structural motif in cholera toxin to activate an unfolded protein response.The Journal of cell biology · 2024Article
- Article
- Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection.Current issues in molecular biology · 2024Review
- Positive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution.Nature communications · 2024Article
- SARS-CoV-2 and innate immunity: the good, the bad, and the "goldilocks".Cellular & molecular immunology · 2024Review
- SARS-CoV-2 ORF8 as a Modulator of Cytokine Induction: Evidence and Search for Molecular Mechanisms.Viruses · 2024Review
- SARS-CoV-2 Accessory Protein Orf7b Induces Lung Injury via c-Myc Mediated Apoptosis and Ferroptosis.International journal of molecular sciences · 2024Article
22 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The open reading frame 8 (orf8) is an accessory protein of SARS-CoV-2. It has 121 amino acids with two genotypes, orf8L and orf8S. In this study, we overexpressed the orf8L and orf8S of SARS-CoV-2 as well as the orf8b of SARS-CoV to investigate their roles in the regulation of endoplasmic reticulum (ER) stress and the inhibition of interferon beta (IFNß) production. We found that the two genotypes of SARS-CoV-2 orf8 are capable of inducing ER stress without significant difference by triggering the activating transcription factor 6 (ATF6) and inositol-requiring enzymes 1 (IRE1) branches of the ER stress pathway. However, the third branch of ER stress pathway, i.e. the protein kinase-like ER kinase (PERK), was unaffected by the overexpression of SARS-CoV-2 orf8L or orf8S. Moreover, both orf8L and orf8S of SARS-CoV-2 are capable of down regulating the production of IFNß and interferon-stimulated genes (ISG), ISG15 and ISG56 induced by polyinosinic-polycytidylic acid (poly (I:C)). Moreover, we also found decreased nuclear translocation of Interferon regulatory factor 3 (IRF3), after overexpressing orf8L and orf8S induced by poly (I:C). Our data demonstrated that SARS-CoV-2 orf8 protein could induce ER stress by activating the ATF6 and IRE1 pathways, but not the PERK pathway, and functions as an interferon antagonist to inhibit the production of IFNß. However, these functions appeared not to be affected by the genotypes of SARS-CoV-2 orf8L and orf8S.
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