Role of CARD Region of MDA5 Gene in Canine Influenza Virus Infection

Fu, Cheng; Ye, Shaotang; Liu, Yongbo; Li, Shoujun

doi:10.3390/v12030307

Cited by 10 publications

(9 citation statements)

References 57 publications

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“…Our study suggests that selective and highly efficient removal of MDA5-Ab in plasma could benefit the patient. MDA5 is a member of the RIG-I–like receptor family that induces the body’s immune response and plays an antiviral role [ 36 , 37 ]. As a signalling domain on MDA5, 2CARD recruits the downstream adaptor MAVS, which signals through the TRAF3/TBK1 and TRAF6/IKK pathways to activate the transcription factors IRF3 and NF-κB and promote proinflammatory factor and IFN cytokine expression, enabling the cells to achieve antiviral status [ 38 , 39 ].…”

Section: Discussionmentioning

confidence: 99%

The central helicase domain holds the major conformational epitopes of melanoma differentiation–associated gene 5 autoantibodies

Yan

Peng

et al. 2023

Rheumatology

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Objectives Autoantibodies against MDA5 serve as a biomarker for dermatomyositis (DM) and a risk factor for interstitial lung disease (ILD). MDA5 is a protein responsible for sensing RNA virus infection and activating signalling pathways against it. However, little is known about antigen epitopes on MDA5 autoantibodies. We aimed to determine the interaction of the MDA5 autoantibody-antigen epitope. Methods Cell-based assays (CBAs), immunoprecipitation-immunoblot assays, and various immunoblotting techniques were used in the study. Results We demonstrate that DM patient autoantibodies recognize MDA5 epitopes in a native conformation-dependent manner. Furthermore, we identified the central helicase domain formed by Hel1, Hel2i, Hel2, and pincer (3Hel) as the major epitopes. As proof of principle, the purified 3Hel efficiently absorbed MDA5 autoantibodies from patient sera through immunoprecipitation-immunoblot assay. Conclusion Our study uncovers the nature of antigen epitopes on MDA5 and provides guidance for diagnosis and targeted therapeutic approach development.

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Section: Discussionmentioning

confidence: 99%

The central helicase domain holds the major conformational epitopes of melanoma differentiation–associated gene 5 autoantibodies

Yan

Peng

et al. 2023

Rheumatology

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“…RIG-I and MDA5 contain a DExD/H-box RNA helicase domain, a C-terminal inhibitory domain (RD), and two tandem caspase recruitment domains (CARDs) at the N terminus, whereas LGP2 lacks CARDs domains (Jia et al, 2021). LGP2 reported to regulate RIG-I and MDA5 depending on the type of infectious RNA virus (Fu et al, 2020;Kong et al, 2021). Mitochondrial antiviral-signaling protein (MAVS) is a CARD domain-containing transmembrane protein localized to the outer mitochondrial membrane.…”

Section: Rig-i Pathway Against Virusesmentioning

confidence: 99%

Crosstalk between mitophagy and innate immunity in viral infection

Chen

Liu

et al. 2022

Front. Microbiol.

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Mitochondria are important organelles involved in cell metabolism and programmed cell death in eukaryotic cells and are closely related to the innate immunity of host cells against viruses. Mitophagy is a process in which phagosomes selectively phagocytize damaged or dysfunctional mitochondria to form autophagosomes and is degraded by lysosomes, which control mitochondrial mass and maintain mitochondrial dynamics and cellular homeostasis. Innate immunity is an important part of the immune system and plays a vital role in eliminating viruses. Viral infection causes many physiological and pathological alterations in host cells, including mitophagy and innate immune pathways. Accumulating evidence suggests that some virus promote self-replication through regulating mitophagy-mediated innate immunity. Clarifying the regulatory relationships among mitochondria, mitophagy, innate immunity, and viral infection will shed new insight for pathogenic mechanisms and antiviral strategies. This review systemically summarizes the activation pathways of mitophagy and the relationship between mitochondria and innate immune signaling pathways, and then discusses the mechanisms of viruses on mitophagy and innate immunity and how viruses promote self-replication by regulating mitophagy-mediated innate immunity.

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“…The innate immune response, often known as non-specific immunity, is the body's first line of defense ( 1 ) and recognizes pathogen-associated molecular patterns (PAMPs) and host-derived danger-associated molecular patterns (DAMPs) via pattern recognition receptors (PRRs) ( 2 ). NOD-like receptors (NLRs), which belong to the evolutionarily well conserved PRR family are located in the cytoplasm.…”

Section: Introductionmentioning

confidence: 99%

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

et al. 2023

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The inflammasome regulates innate immunity by serving as a signaling platform. The Nod-like receptor protein 3 (NLRP3) inflammasome, equipped with NLRP3, the adaptor protein apoptosis-associated speck-like protein (ASC) and pro-caspase-1, is by far the most extensively studied and well-characterized inflammasome. A variety of stimuli can activate the NLRP3 inflammasome. When activated, the NLRP3 protein recruits the adaptor ASC protein and activates pro-caspase-1, resulting in inflammatory cytokine maturation and secretion, which is associated with inflammation and pyroptosis. However, the aberrant activation of the NLRP3 inflammasome has been linked to various inflammatory diseases, including atherosclerosis, ischemic stroke, Alzheimer's disease, diabetes mellitus and inflammatory bowel disease. Therefore, the NLRP3 inflammasome has emerged as a promising therapeutic target for inflammatory diseases. In the present review, systematic searches were performed using 'NLRP3 inhibitor(s)' and 'inflammatory disease(s)' as key words. By browsing the literature from 2012 to 2022, 100 articles were retrieved, of which 35 were excluded as they were reviews, editorials, retracted or unavailable online, and 65 articles were included. According to the retrieved literature, the current understanding of NLRP3 inflammasome pathway activation in inflammatory diseases was summarize, and inhibitors of the NLRP3 inflammasome pathway targeting the NLRP3 protein and other inflammasome components or products were highlighted. Additionally, the present review briefly discusses the current novel efforts in clinical research.

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Role of CARD Region of MDA5 Gene in Canine Influenza Virus Infection

Cited by 10 publications

References 57 publications

The central helicase domain holds the major conformational epitopes of melanoma differentiation–associated gene 5 autoantibodies

The central helicase domain holds the major conformational epitopes of melanoma differentiation–associated gene 5 autoantibodies

Crosstalk between mitophagy and innate immunity in viral infection

Inhibitors of the NLRP3 inflammasome pathway as promising therapeutic candidates for inflammatory diseases (Review)

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