ArticlemBio2022
SARS-CoV-2 Diverges from Other Betacoronaviruses in Only Partially Activating the IRE1α/XBP1 Endoplasmic Reticulum Stress Pathway in Human Lung-Derived Cells.
Article in mBio, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- IRE1α Is Associated with Host Lipid Biosynthesis During Human Coronavirus OC43 Infection.Viruses · 2026Article
- Chemical modulation of the unfolded protein response reveals an antiviral role for the PERK pathway in human coronavirus 229E infection.RSC chemical biology · 2026Article
- RNase L Regulates Antiviral Responsiveness through Cleavage of XBP1 mRNA.bioRxiv : the preprint server for biology · 2026Article
- Dual-function cytokines as modulators of autophagy: reprogramming inflammatory resolution in severe COVID-19.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Endoplasmic reticulum stress-mediated cell death in spinal cord injury: from molecular mechanisms to therapeutic applications.Frontiers in cell and developmental biology · 2026Review
- Cell type-specific eQTL analysis of COVID-19 based on single-cell transcriptomic data.NAR genomics and bioinformatics · 2025Article
- Optogenetic Clustering of Human IRE1 Reveals Differential Regulation of Transcription and mRNA Splice Isoform Abundance by the UPR.bioRxiv : the preprint server for biology · 2025Article
- IRE1α promotes phagosomal calcium flux to enhance macrophage fungicidal activity.Cell reports · 2025Article
- Human coronaviruses: activation and antagonism of innate immune responses.Microbiology and molecular biology reviews : MMBR · 2025Review
- Article
- A portrait of the infected cell: how SARS-CoV-2 infection reshapes cellular processes and pathways.Npj viruses · 2024Review
- Equivocating and Deliberating on the Probability of COVID-19 Infection Serving as a Risk Factor for Lung Cancer and Common Molecular Pathways Serving as a Link.Pathogens (Basel, Switzerland) · 2024Review
- Review
- Activation of alveolar epithelial ER stress by β-coronavirus infection disrupts surfactant homeostasis in mice: implications for COVID-19 respiratory failure.American journal of physiology. Lung cellular and molecular physiology · 2024Article
- The IRE1α-XBP1 arm of the unfolded protein response is a host factor activated in SARS-CoV-2 infection.Biochimica et biophysica acta. Molecular basis of disease · 2024Article
- Insights into the Activation of Unfolded Protein Response Mechanism during Coronavirus Infection.Current issues in molecular biology · 2024Review
- Non-canonical activation of IRE1α duringbioRxiv : the preprint server for biology · 2024Article
- Article
- Human Betacoronavirus OC43 Interferes with the Integrated Stress Response Pathway in Infected Cells.Viruses · 2024Article
- Improved Culture Methods for Human Coronaviruses HCoV-OC43, HCoV-229E, and HCoV-NL63.Current protocols · 2023Article
Corrections and comments
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Authors and funding
25 authors at 3 institutions in 1 country.
Funding
Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has killed over 6 million individuals worldwide and continues to spread in countries where vaccines are not yet widely available or its citizens are hesitant to become vaccinated. Therefore, it is critical to unravel the molecular mechanisms that allow SARS-CoV-2 and other coronaviruses to infect and overtake the host machinery of human cells. Coronavirus replication triggers endoplasmic reticulum (ER) stress and activation of the unfolded protein response (UPR), a key host cell pathway widely believed to be essential for viral replication. We examined the master UPR sensor IRE1α kinase/RNase and its downstream transcription factor effector XBP1s, which is processed through an IRE1α-mediated mRNA splicing event, in human lung-derived cells infected with betacoronaviruses. We found that human respiratory coronavirus OC43 (HCoV-OC43), Middle East respiratory syndrome coronavirus (MERS-CoV), and murine coronavirus (MHV) all induce ER stress and strongly trigger the kinase and RNase activities of IRE1α as well as XBP1 splicing. In contrast, SARS-CoV-2 only partially activates IRE1α through autophosphorylation, but its RNase activity fails to splice XBP1. Moreover, while IRE1α was dispensable for replication in human cells for all coronaviruses tested, it was required for maximal expression of genes associated with several key cellular functions, including the interferon signaling pathway, during SARS-CoV-2 infection. Our data suggest that SARS-CoV-2 actively inhibits the RNase of autophosphorylated IRE1α, perhaps as a strategy to eliminate detection by the host immune system.
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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.