ArticleMicrobiology spectrum2022
Ubiquitination of SARS-CoV-2 ORF7a Prevents Cell Death Induced by Recruiting BclXL To Activate ER Stress.
Article in Microbiology spectrum, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 18 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- Article
- HERPUD1 suppresses porcine epidemic diarrhea virus replication by recruiting HRD1 to degrade viral ORF3 protein.Journal of virology · 2026Article
- SADS-CoV NS3 induces apoptosis by blocking the formation of Bcl-xL-BAK complex.Journal of virology · 2026Article
- A murine coronavirus infection platform identifies proviral and proinflammatory activities of SARS-CoV-2 accessory protein 7a.Journal of virology · 2026Article
- The roles of post-translational modifications in the pathogenesis of RNA viruses: allies or adversaries?Frontiers in microbiology · 2026Review
- Rewriting the viral script: post-translational modifications orchestrating SARS-CoV-2 pathogenesis and immune evasion.Frontiers in microbiology · 2026Review
- SARS-CoV-2 ORF7a Protein Impedes Type I Interferon-Activated JAK/STAT Signaling by Interacting with HNRNPA2B1.International journal of molecular sciences · 2025Article
- Impact of SARS-CoV-2 Wuhan and Omicron Variant Proteins on Type I Interferon Response.Viruses · 2025Article
- Hidden players of COVID-19: the evolving roles of SARS-CoV-2 accessory proteins.Frontiers in immunology · 2025Review
- Live imaging of airway epithelium reveals that mucociliary clearance modulates SARS-CoV-2 spread.Nature communications · 2024Article
- A glimpse into viral warfare: decoding the intriguing role of highly pathogenic coronavirus proteins in apoptosis regulation.Journal of biomedical science · 2024Review
- Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection.Current issues in molecular biology · 2024Review
- Ubiquitin Ligase Parkin Regulates the Stability of SARS-CoV-2 Main Protease and Suppresses Viral Replication.ACS infectious diseases · 2024Article
- SARS-CoV-2 ORF7a Mutation Found in BF.5 and BF.7 Sublineages Impacts Its Functions.International journal of molecular sciences · 2024Article
- The role of cell death in SARS-CoV-2 infection.Signal transduction and targeted therapy · 2023Review
- Evaluation of SARS-CoV-2 ORF7a Deletions from COVID-19-Positive Individuals and Its Impact on Virus Spread in Cell Culture.Viruses · 2023Article
- Role of E3 ubiquitin ligases and deubiquitinating enzymes in SARS-CoV-2 infection.Frontiers in cellular and infection microbiology · 2023Review
- Contribution to pathogenesis of accessory proteins of deadly human coronaviruses.Frontiers in cellular and infection microbiology · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
12 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19), which has emerged in the last 2 years. The accessory protein ORF7a has been proposed as an immunomodulating factor that can cause dramatic inflammatory responses, but it is unknown how ORF7a interacts with host cells. We show that ORF7a induces cell apoptosis by recruiting the prosurvival factor BclXL to the endoplasmic reticulum (ER) via the exposed C-terminal residues Lys117 and Lys119. Simultaneously, ORF7a activates ER stress via the PERK-elF2α-CHOP pathway and inhibits the expression of endogenous BclXL, resulting in enhanced cell apoptosis. Ubiquitination of ORF7a interrupts the interaction with BclXL in the ER and weakens the activation of ER stress, which to some extent rescues the cells. Our work demonstrates that SARS-CoV-2 ORF7a hires antiapoptosis protein and aggregates on the ER, resulting in ER stress and apoptosis initiation. On the other hand, ORF7a utilizes the ubiquitin system to impede and escape host elimination, providing a promising potential target for developing strategies for minimizing the COVID-19 pandemic.
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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.