ArticlePLoS pathogens2017
iRhom2 is essential for innate immunity to RNA virus by antagonizing ER- and mitochondria-associated degradation of VISA.
Article in PLoS pathogens, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 49 citations in OpenAlex.
- Congenital iRHOM2 deficiency causes ADAM17 dysfunction and environmentally directed immunodysregulatory disease.Nature immunology · 2022Trial
- Targeting iRhom2-mediated PANoptosis ameliorates acute kidney injury.Acta pharmacologica Sinica · 2026Article
- Neuroinflammation and blood-brain barrier disruption in Japanese encephalitis virus infection: mechanisms, therapeutic targets, and intervention strategies.Archives of pharmacal research · 2026Review
- An additional site mutation in MITA/STING gain-of-function mutants abolishes the autoimmune SAVI phenotypes and directs a therapeutic strategy.Cell insight · 2026Article
- Physalin F Promotes AFG3L2-Mediated Degradation of VISA/MAVS to Suppress Innate Immune Response to RNA Virus.Pathogens (Basel, Switzerland) · 2026Article
- The role of ER-associated degradation and ER-phagy in health and disease.Signal transduction and targeted therapy · 2026Review
- Holding Out for a Model: Rhomboid Superfamily in Vertebrate Development and Disease.Journal of cellular physiology · 2025Review
- ZebrafishJournal of virology · 2024Article
- iRhom2 regulates ectodomain shedding and surface expression of the major histocompatibility complex (MHC) class I.Cellular and molecular life sciences : CMLS · 2024Article
- Advances in the study of protein folding and endoplasmic reticulum-associated degradation in mammal cells.Journal of Zhejiang University. Science. B · 2024Review
- Mitochondrial DNA-triggered innate immune response: mechanisms and diseases.Cellular & molecular immunology · 2023Review
- The Role of the Rhomboid Superfamily in ER Protein Quality Control: From Mechanisms and Functions to Diseases.Cold Spring Harbor perspectives in biology · 2023Review
- Review
- RNF5: inhibiting antiviral immunity and shaping virus life cycle.Frontiers in immunology · 2023Review
- E3 ubiquitin ligase RNF5 attenuates pathological cardiac hypertrophy through STING.Cell death & disease · 2022Article
- iRhom pseudoproteases regulate ER stress-induced cell death through IPNature communications · 2022Article
- The transmembrane endoplasmic reticulum-associated E3 ubiquitin ligase TRIM13 restrains the pathogenic-DNA-triggered inflammatory response.Science advances · 2022Article
- Inflammatory activation of surface molecule shedding by upregulation of the pseudoprotease iRhom2 in colon epithelial cells.Scientific reports · 2021Article
- Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors.Cellular & molecular immunology · 2021Review
- iRhom2: An Emerging Adaptor Regulating Immunity and Disease.International journal of molecular sciences · 2020Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
VISA (also known as MAVS, IPS-1 and Cardif) is an essential adaptor protein in innate immune response to RNA virus. The protein level of VISA is delicately regulated before and after viral infection to ensure the optimal activation and timely termination of innate antiviral response. It has been reported that several E3 ubiquitin ligases can mediate the degradation of VISA, but how the stability of VISA is maintained before and after viral infection remains enigmatic. In this study, we found that the ER-associated inactive rhomboid protein 2 (iRhom2) plays an essential role in mounting an efficient innate immune response to RNA virus by maintaining the stability of VISA through distinct mechanisms. In un-infected and early infected cells, iRhom2 mediates auto-ubiquitination and degradation of the E3 ubiquitin ligase RNF5 and impairs the assembly of VISA-RNF5-GP78 complexes, thereby antagonizes ER-associated degradation (ERAD) of VISA. In the late phase of viral infection, iRhom2 mediates proteasome-dependent degradation of the E3 ubiquitin ligase MARCH5 and impairs mitochondria-associated degradation (MAD) of VISA. Maintenance of VISA stability by iRhom2 ensures efficient innate antiviral response at the early phase of viral infection and ready for next round of response. Our findings suggest that iRhom2 acts as a checkpoint for the ERAD/MAD of VISA, which ensures proper innate immune response to RNA virus.
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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.