ArticleThe Journal of cell biology2022
SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2ZYG11B activity.
Article in The Journal of cell biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 46 citations in OpenAlex.
- Neuron-intrinsic and glial pathways regulate sensory cilia regeneration in adultbioRxiv : the preprint server for biology · 2026Article
- Structure of the E3 ligase CRL2Cell reports · 2026Article
- Targeting SARS-CoV-2 Structural and Accessory Proteins: Emerging Opportunities for Small-Molecule Coronavirus Antivirals.Pharmaceutics · 2026Review
- Structures of ZYG11B-EloB-EloC-substrate complex reveal mechanisms of CRL2Nature communications · 2026Article
- Host transcriptomic analysis reveals a defective intracellular environment that limits SARS-CoV-2 replication in CFTR-deficient airway epithelium.Frontiers in cellular and infection microbiology · 2026Article
- Importance of De Novo Gene Evolution to Emerging Viral Threats: The ORF10 Strain-Restricted Orphan Gene of SARS-CoV-2 Promotes Pathogenesis.Molecular biology and evolution · 2025Article
- Coronavirus M protein impairs cilium during early infection by enhancing the AurA-HDAC6 axis.PLoS pathogens · 2025Article
- ZYG11B suppresses multiple enteroviruses by triggering viral VP1 degradation.Journal of virology · 2025Article
- A comprehensive review of current insights into the virulence factors of SARS-CoV-2.Journal of virology · 2025Review
- PROS1 released by lung basal cells limits inflammation in epithelial and monocytes during SARS-CoV-2 infection.Discovery immunology · 2025Article
- Human E3 ubiquitin ligases: accelerators and brakes for SARS-CoV-2 infection.Biochemical Society transactions · 2024Review
- SARS-CoV-2 ORF10 hijacking ubiquitination machinery reveals potential unique drug targeting sites.Acta pharmaceutica Sinica. B · 2024Article
- Rare host variants in ciliary expressed genes contribute to COVID-19 severity in Bulgarian patients.Scientific reports · 2024Article
- Review
- Chlamydia trachomatis induces disassembly of the primary cilium to promote the intracellular infection.PLoS pathogens · 2024Article
- SARS-CoV-2 variant of concern fitness and adaptation in primary human airway epithelia.Cell reports · 2024Article
- 1-L Transcription of SARS-CoV-2 Spike Protein S1 Subunit.International journal of molecular sciences · 2024Article
- Ubiquitin Ligase Parkin Regulates the Stability of SARS-CoV-2 Main Protease and Suppresses Viral Replication.ACS infectious diseases · 2024Article
- Article
- COVID-19 Causes Ciliary Dysfunction as Demonstrated by Human Intranasal Micro-Optical Coherence Tomography Imaging.American journal of respiratory cell and molecular biology · 2023Article
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Authors and funding
24 authors at 5 institutions in 1 country.
Funding
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the ongoing global pandemic of coronavirus disease 2019 (COVID-19). Loss of smell and taste are symptoms of COVID-19, and may be related to cilia dysfunction. Here, we found that the SARS-CoV-2 ORF10 increases the overall E3 ligase activity of the CUL2ZYG11B complex by interacting with ZYG11B. Enhanced CUL2ZYG11B activity by ORF10 causes increased ubiquitination and subsequent proteasome-mediated degradation of an intraflagellar transport (IFT) complex B protein, IFT46, thereby impairing both cilia biogenesis and maintenance. Further, we show that exposure of the respiratory tract of hACE2 mice to SARS-CoV-2 or SARS-CoV-2 ORF10 alone results in cilia-dysfunction-related phenotypes, and the ORF10 expression in primary human nasal epithelial cells (HNECs) also caused a rapid loss of the ciliary layer. Our study demonstrates how SARS-CoV-2 ORF10 hijacks CUL2ZYG11B to eliminate IFT46 and leads to cilia dysfunction, thereby offering a powerful etiopathological explanation for how SARS-CoV-2 causes multiple cilia-dysfunction-related symptoms specific to COVID-19.
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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.