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: Alpinone is a flavonoid obtained from the resinous exudate of Heliotropium huascoense as discussed by the authors, which shows antiviral activity against the infectious salmon anemia virus (ISAV), which causes severe disease in farmed Atlantic salmon.
Abstract: Alpinone is a flavonoid obtained from the resinous exudate of Heliotropium huascoense. This flavonoid shows antiviral activity against the infectious salmon anemia virus (ISAV), which causes severe disease in farmed Atlantic salmon. Here, we aim to elucidate mechanisms underlying the antiviral effects of the flavonoid. In this regard, we evaluated whether Alpinone can act upregulating the pattern-recognition receptor genes, i.e., the RIG-I-like, TLR3, and TLR9 genes, and the genes of the downstream signaling pathways. Transcriptional expression of the genes was analyzed using real-time PCR after 8, 24, and 48 h treatment of salmon kidney adherent cells with 15 μg/mL of Alpinone. First, we showed that Alpinone induced IFNa expression in the kidney adherent cells, indicating that this type of salmon cells is in part responsible for the effects previously reported in vivo. Upregulation of the IFN-induced myxovirus resistance (Mx) gene was also observed in the head kidney cells in response to the treatment. Overexpression reached a maximum level at 24 h post-treatment. Interestingly, Alpinone also induced upregulation of the cytosolic receptors of ssRNA, named Retinoic acid-inducible gene I (RIG-I) and Melanoma Differentiation-Associated protein 5 (MDA5), but there were no effects on the transcriptional expression of the TLR3 and TLR9 endosomal receptors. In addition, Alpinone upregulated the expression of genes encoding the main components of the RIG-I/MDA5 signaling pathways, such as the mitochondrial antiviral-signaling protein (MAVS), TNF Receptor Associated Factor 3 (TRAF3), TANK-binding kinase 1 (TBK1), I-kappaB kinase e (IKKe), the transcription factors IRF-3, and IRF7. The increased expression of all these genes is consistent with the upregulation of IFNa and Mx mRNAs. Because BX795 completely prevents Alpinone-dependent upregulation of IFNa and IRF3, the flavonoid targets seem to be upstream of the kinases TBK1 and IKKe. Altogether, this study contributes to elucidating the mechanisms involved in Alpinone antiviral activity in fish. Alpinone can be used to counteract virus mechanisms of evasion where the onset of interferon-mediated response is prevented or delayed.
2 citations
TL;DR: In this article, the authors developed a human cell line that stably expresses MDA5 and evaluated its analytical performance in order to detect anti-MDA5 Abs by the utilization of indirect immunofluorescence (IIF).
Abstract: Anti-melanoma differentiation-associated protein 5 (MDA5) antibody (Ab) positive dermatomyositis (anti-MDA5 DM) is a rare systemic autoimmune disease; further, its prognosis can be rapidly fatal due to pulmonary involvement. The identification and quantification of anti-MDA5 Abs, which serve as a highly specific biomarker of the disease, is a critical step for the establishing of both the diagnosis and monitoring of the disease’s activity. The development of a simple, fast, low-cost, and specific detection system of anti-MDA5 Ab is therefore highly desirable for the purposes of routine laboratory diagnosis. Here, we developed a human cell line that stably expresses MDA5 and evaluated its analytical performance in order to detect anti-MDA5 Abs by the utilization of indirect immunofluorescence (IIF). Serum samples from 23 anti-MDA5 DM patients and 22 anti-MDA5 Abs negative myositis readings, which were obtained at time of diagnosis, were analyzed by IIF on MDA5-transfected cells. The results were compared with those obtained with specific semi-quantitative (immunodot) and quantitative (ELISA) assays. A specific cytoplasmic pattern was found solely with the sera of anti-MDA5 DM patients. The sensitivity and specificity of IIF on MDA5-transfected cells were 96% and 100%, respectively, compared with ELISA. The anti-MDA5 Abs titers that were determined by this approach were consistent with the quantitative results obtained by ELISA. Baseline concentrations of anti-MDA5 Abs, either by ELISA or IIF, were not significantly different between surviving and deceased patients; further, they did not differ significantly according to clinical phenotypes. Overall, an IIF cell-based assay constitutes a simple, fast, and low-cost approach to identify and quantify anti-MDA5 Abs; moreover, it is as efficient as ELISA.
2 citations
TL;DR: RNF144B negatively regulates antiviral immunity by targeting MDA5 for autophagic degradation through K27/K33-linked polyubiquitination, promoting IFN production and inhibiting EMCV replication in vivo, and enhancing overall survival rate in infected mice.
Abstract: Abstract As a RIG-I-like receptor, MDA5 plays a critical role in antiviral innate immunity by acting as a cytoplasmic double-stranded RNA sensor capable of initiating type I interferon pathways. Here, we show that RNF144B specifically interacts with MDA5 and promotes K27/K33-linked polyubiquitination of MDA5 at lysine 23 and lysine 43, which promotes autophagic degradation of MDA5 by p62. Rnf144b deficiency greatly promotes IFN production and inhibits EMCV replication in vivo. Importantly, Rnf144b −/− mice has a significantly higher overall survival rate than wild-type mice upon EMCV infection. Collectively, our results identify RNF144B as a negative regulator of innate antiviral response by targeting CARDs of MDA5 and mediating autophagic degradation of MDA5.
2 citations
TL;DR: In this article , the attenuation of regulatory T cell (Treg) function by type I IFN signaling in a mouse model expressing a gain-of-function MDA5 G821S mutant was revealed.
2 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2025 | 44 |
| 2024 | 75 |
| 2023 | 80 |
| 2022 | 127 |
| 2021 | 55 |
| 2020 | 53 |