Topic
MDA5
About: MDA5 is a research topic. Over the lifetime, 740 publications have been published within this topic receiving 80681 citations. The topic is also known as: DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide & MDA-5.
Papers published on a yearly basis
Papers
TL;DR: Wang et al. as discussed by the authors reported that SARS-CoV-2 nsp12, the viral RNA-dependent RNA polymerase (RdRp), suppresses host antiviral responses.
Abstract: SARS-CoV-2 is the pathogenic agent of COVID-19, which has evolved into a global pandemic. Compared with some other respiratory RNA viruses, SARS-CoV-2 is a poor inducer of type I interferon (IFN). Here, we report that SARS-CoV-2 nsp12, the viral RNA-dependent RNA polymerase (RdRp), suppresses host antiviral responses. SARS-CoV-2 nsp12 attenuated Sendai virus (SeV)- or poly(I:C)-induced IFN-β promoter activation in a dose-dependent manner. It also inhibited IFN promoter activation triggered by RIG-I, MDA5, MAVS, and IRF3 overexpression. Nsp12 did not impair IRF3 phosphorylation but suppressed the nuclear translocation of IRF3. Mutational analyses suggested that this suppression was not dependent on the polymerase activity of nsp12. Given these findings, our study reveals that SARS-CoV-2 RdRp can antagonize host antiviral innate immunity and thus provides insights into viral pathogenesis.
129 citations
TL;DR: It is shown that the mammalian SID-1 ortholog, SIDT2, is required to transport internalized extracellular dsRNA from endocytic compartments into the cytoplasm for immune activation, and this transport is important for antiviral immunity.
129 citations
TL;DR: The current understanding of endogenous negative regulation in R LR signaling is reviewed and direct inhibition of RLR signaling by viruses as a host immune evasion strategy is explored.
128 citations
TL;DR: How Src activation by TLR3 changes cell migration, adhesion, and proliferation rates and how IRF-3 activation by RLR triggers a gene induction-independent pro-apoptotic pathway that provides strong antiviral protection are discussed.
Abstract: Double-stranded (ds) RNA has diverse roles in host defense and disease prevention. dsRNA, produced by viral replication, elicits strong antiviral responses in host; similar protective responses can also be triggered by cellular dsRNA produced by necrotic, apoptotic, or otherwise stressed, uninfected cells. dsRNA is recognized in the cell by a large family of dsRNA-binding proteins, among which are the pattern recognition receptors (PRRs), toll-like receptor 3 (TLR3), and retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs). TLR3 signals from the endosomal membrane where it senses extracellular dsRNA that has been endocytosed, whereas RLRs signal from the cytoplasm using a mitochondrial adaptor protein. In this review, we will summarize the signaling pathways used by these 2 PRRs, which lead to the activation of specific transcription factors and the induction of many proinflammatory and antiviral genes. However, it is becoming increasingly clear that all host responses are not mediated by the products of these induced genes; signal-dependent post-translational modifications of existing proteins can also profoundly change cellular properties. We will discuss how Src activation by TLR3 changes cell migration, adhesion, and proliferation rates and how IRF-3 activation by RLR triggers a gene induction-independent pro-apoptotic pathway that provides strong antiviral protection.
126 citations
TL;DR: The unique mechanism by which DI particles trigger the maturation of DCs represents a novel strategy that could be further exploited for the development of potent adjuvant molecules.
Abstract: Defective interfering (DI) particles are byproducts of virus replication that potently enhance dendritic cell (DC) maturation by virus infection. DI particles have been reported for many different viruses and are strong inducers of type I IFNs. The cellular mechanisms involved in the response to DI particles are not known. In this study, we show that 1) DI particles are recognized by more than one viral sensor independently of TLRs and type I IFN signaling; 2) The helicase MDA5 participates in the detection of DI genomes as MDA5-deficient DCs respond inefficiently to Sendai virus stocks containing DI particles; 3) DI particles stimulate the expression of IRF3-responsive genes by a uniquely potent mechanism when compared with other prototypic viral stimulus; and 4) the efficient detection of DI particles overcomes virus immune antagonism. These data highlight the outstanding adjuvant capacity of DI particles in stimulating mouse and human DCs. They also offer biological relevance to the previously reported inhibition of MDA5 by different paramyxovirus V proteins. The unique mechanism by which DI particles trigger the maturation of DCs represents a novel strategy that could be further exploited for the development of potent adjuvant molecules.
126 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 44 |
| 2024 | 75 |
| 2023 | 80 |
| 2022 | 127 |
| 2021 | 55 |
| 2020 | 53 |