ArticlePLoS pathogens2013
Cytomegalovirus downregulates IRE1 to repress the unfolded protein response.
Article in PLoS pathogens, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 62 citations in OpenAlex.
- Mechanisms and Determinants of CMV Reactivation in Kidney Transplantation.International journal of molecular sciences · 2026Review
- Targeting the UPR with Small Molecules: Emerging Strategies for Immune Regulation.Molecules (Basel, Switzerland) · 2026Review
- Dynamic Modulation of IRE1α-XBP1 Signaling by Adenovirus.Pathogens (Basel, Switzerland) · 2025Article
- Dynamic modulation of IRE1α-XBP1 signaling by adenovirus.bioRxiv : the preprint server for biology · 2024Article
- Paneth cell TNF signaling induces gut bacterial translocation and sepsis.Cell host & microbe · 2024Article
- Viral Infections and Their Ability to Modulate Endoplasmic Reticulum Stress Response Pathways.Viruses · 2024Review
- The roles and mechanisms of endoplasmic reticulum stress-mediated autophagy in animal viral infections.Veterinary research · 2024Review
- The battle between host antiviral innate immunity and immune evasion by cytomegalovirus.Cellular and molecular life sciences : CMLS · 2024Review
- Uncloaking the viral glycocalyx: How do viruses exploit glycoimmune checkpoints?Advances in virus research · 2024Review
- The gp130/STAT3-endoplasmic reticulum stress axis regulates hepatocyte necroptosis in acute liver injury.Croatian medical journal · 2023Article
- Comparative Proteomic Analysis Provides New Insights into the Molecular Basis of Thermal-Induced Parthenogenesis in Silkworm (Insects · 2023Article
- Ebola Virus Activates IRE1α-DependentViruses · 2022Article
- Model Identifies Genetic Predisposition of Alzheimer's Disease as Key Decider in Cell Susceptibility to Stress.International journal of molecular sciences · 2021Article
- The endoplasmic reticulum unfolded protein response - homeostasis, cell death and evolution in virus infections.FEMS microbiology reviews · 2021Review
- Viral mediated tethering to SEL1L facilitates ER-associated degradation of IRE1.Journal of virology · 2021Article
- Pharmacological Inhibition of IRE-1 Alpha Activity in Herpes Simplex Virus Type 1 and Type 2-Infected Dendritic Cells Enhances T Cell Activation.Frontiers in immunology · 2021Article
- NOD1 and NOD2 Activation by Diverse Stimuli: a Possible Role for Sensing Pathogen-Induced Endoplasmic Reticulum Stress.Infection and immunity · 2020Review
- The Human Cytomegalovirus Transmembrane Protein pUL50 Induces Loss of VCP/p97 and Is Regulated by a Small Isoform of pUL50.Journal of virology · 2020Article
- Morphology Remodeling and Selective Autophagy of Intracellular Organelles during Viral Infections.International journal of molecular sciences · 2020Review
- Activation of PERK-ATF4-CHOP pathway as a novel therapeutic approach for efficient elimination of HTLV-1-infected cells.Blood advances · 2020Article
Corrections and comments
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Authors and funding
10 authors at 6 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During viral infection, a massive demand for viral glycoproteins can overwhelm the capacity of the protein folding and quality control machinery, leading to an accumulation of unfolded proteins in the endoplasmic reticulum (ER). To restore ER homeostasis, cells initiate the unfolded protein response (UPR) by activating three ER-to-nucleus signaling pathways, of which the inositol-requiring enzyme 1 (IRE1)-dependent pathway is the most conserved. To reduce ER stress, the UPR decreases protein synthesis, increases degradation of unfolded proteins, and upregulates chaperone expression to enhance protein folding. Cytomegaloviruses, as other viral pathogens, modulate the UPR to their own advantage. However, the molecular mechanisms and the viral proteins responsible for UPR modulation remained to be identified. In this study, we investigated the modulation of IRE1 signaling by murine cytomegalovirus (MCMV) and found that IRE1-mediated mRNA splicing and expression of the X-box binding protein 1 (XBP1) is repressed in infected cells. By affinity purification, we identified the viral M50 protein as an IRE1-interacting protein. M50 expression in transfected or MCMV-infected cells induced a substantial downregulation of IRE1 protein levels. The N-terminal conserved region of M50 was found to be required for interaction with and downregulation of IRE1. Moreover, UL50, the human cytomegalovirus (HCMV) homolog of M50, affected IRE1 in the same way. Thus we concluded that IRE1 downregulation represents a previously undescribed viral strategy to curb the UPR.
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