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http://dx.doi.org/10.1007/s10875-024-01813-7 | DOI Listing |
mBio
August 2025
Division of Infectious Diseases, Anschutz Medical Campus, University of Colorado School of Medicine, Aurora, Colorado, USA.
Unlabelled: Sensing of viral double-stranded RNA (dsRNA) by MDA5 triggers abundant but transient interferon-stimulated gene (ISGs) expression. If dsRNA synthesis is made persistent by transgenically expressing a picornaviral RNA-dependent RNA polymerase (RdRp) in mice, lifelong MDA5-MAVS pathway activation and marked, global ISG upregulation result. This confers robust protection from viral diseases, but in contrast to numerous other chronic MDA5 hyperactivation states, the mice suffer no autoimmune or other health consequences.
View Article and Find Full Text PDFAdv Sci (Weinh)
June 2025
Department of Pharmacy, Personalized Drug Therapy Key Laboratory, Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, 610072, China.
The essential cytoplasmic RNA sensor Melanoma Differentiation-Associated protein 5 (MDA5) initiates type I interferons (IFNs) signaling and subsequent immune responses. However, aberrant activation of MDA5 by viral infections or gain-of-function mutations leads to severe autoimmune diseases, for most of which effective treatment is limited. Here, it is shown that inactivation of ubiquitin-specific protease 8 (USP8/UBPy) degrades the MDA5 protein, suppressing antiviral signaling and autoimmunity.
View Article and Find Full Text PDFSensing of viral double-stranded RNA by MDA5 triggers abundant but transient interferon-stimulated gene (ISGs) expression. If dsRNA synthesis is made persistent by transgenically expressing a picornaviral RNA-dependent RNA polymerase (RdRp) in mice, lifelong MDA5-MAVS pathway activation and marked, global ISG upregulation result. This confers robust protection from viral diseases but in contrast to numerous other chronic MDA5 hyperactivation states, the mice suffer no autoimmune or other health consequences.
View Article and Find Full Text PDFJ Immunol
November 2024
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL.
Type 1 diabetes (T1D) is a chronic autoimmune disease that is caused by a combination of genetic and environmental risk factors. In this study, we sought to determine whether a known genetic risk factor, the rs1990760 single nucleotide polymorphism (SNP) (A946T) in IFIH1, resulted in a gain of function in the MDA5 protein and the effects of this mutation on the regulation of type I IFNs during infection with the diabetogenic virus coxsackievirus B3. We found that in cell lines overexpressing the risk variant IFIH1946T there was an elevated level of basal type I IFN signaling and increased basal IFN-stimulated gene expression.
View Article and Find Full Text PDFJ Clin Immunol
October 2024
MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK.