scholarly journals Cellular Deubiquitylating Enzyme: A Regulatory Factor of Antiviral Innate Immunity

2021 ◽  
Vol 12 ◽  
Author(s):  
Sijing Long ◽  
Li Yang ◽  
Wei Dang ◽  
Shuyu Xin ◽  
Mingjuan Jiang ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Innate Immune ◽  
Fine Tuning ◽  
Biological Functions ◽  
Regulatory Factor ◽  
Antiviral Responses ◽  
Pyrin Domain ◽  
Antiviral Innate Immunity ◽  
Nlrp3 Inflammasomes ◽  
Substrate Proteins

Deubiquitylating enzymes (DUBs) are proteases that crack the ubiquitin code from ubiquitylated substrates to reverse the fate of substrate proteins. Recently, DUBs have been found to mediate various cellular biological functions, including antiviral innate immune response mediated by pattern-recognition receptors (PRRs) and NLR Family pyrin domain containing 3 (NLRP3) inflammasomes. So far, many DUBs have been identified to exert a distinct function in fine-tuning antiviral innate immunity and are utilized by viruses for immune evasion. Here, the recent advances in the regulation of antiviral responses by DUBs are reviewed. We also discussed the DUBs-mediated interaction between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and antiviral innate immunity. The understanding of the mechanisms on antiviral innate immunity regulated by DUBs may provide therapeutic opportunities for viral infection.

scholarly journals Fine-Tuning of the RIG-I-Like Receptor/Interferon Regulatory Factor 3-Dependent Antiviral Innate Immune Response by the Glycogen Synthase Kinase 3/β-Catenin Pathway

2015 ◽  
Vol 35 (17) ◽  
pp. 3029-3043 ◽  
Author(s):  
Kashif Aziz Khan ◽  
Florence Dô ◽  
Alexandre Marineau ◽  
Priscilla Doyon ◽  
Jean-François Clément ◽  
...  
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Innate Immune Response ◽  
Glycogen Synthase ◽  
Es Cells ◽  
Interferon Regulatory Factor ◽  
Innate Immune ◽  
Regulatory Factor ◽  
Gsk 3Β ◽  
Antiviral Innate Immunity

Induction of an antiviral innate immune response relies on pattern recognition receptors, including retinoic acid-inducible gene 1-like receptors (RLR), to detect invading pathogens, resulting in the activation of multiple latent transcription factors, including interferon regulatory factor 3 (IRF3). Upon sensing of viral RNA and DNA, IRF3 is phosphorylated and recruits coactivators to induce type I interferons (IFNs) and selected sets of IRF3-regulated IFN-stimulated genes (ISGs) such as those for ISG54 (Ifit2), ISG56 (Ifit1), and viperin (Rsad2). Here, we used wild-type, glycogen synthase kinase 3α knockout (GSK-3α−/−), GSK-3β−/−, and GSK-3α/β double-knockout (DKO) embryonic stem (ES) cells, as well as GSK-3β−/−mouse embryonic fibroblast cells in which GSK-3α was knocked down to demonstrate that both isoforms of GSK-3, GSK-3α and GSK-3β, are required for this antiviral immune response. Moreover, the use of two selective small-molecule GSK-3 inhibitors (CHIR99021 and BIO-acetoxime) or ES cells reconstituted with the catalytically inactive versions of GSK-3 isoforms showed that GSK-3 activity is required for optimal induction of antiviral innate immunity. Mechanistically, GSK-3 isoform activation following Sendai virus infection results in phosphorylation of β-catenin at S33/S37/T41, promoting IRF3 DNA binding and activation of IRF3-regulated ISGs. This study identifies the role of a GSK-3/β-catenin axis in antiviral innate immunity.

scholarly journals Negative Regulation of RNF90 on RNA Virus-Triggered Antiviral Immune Responses Targeting MAVS

2021 ◽  
Vol 12 ◽  
Author(s):  
Bo Yang ◽  
Ge Zhang ◽  
Xiao Qin ◽  
Yulu Huang ◽  
Xiaowen Ren ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Rna Virus ◽  
Ring Finger ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Antiviral Signaling ◽  
Antiviral Responses ◽  
Mitochondrial Antiviral Signaling ◽  
Antiviral Innate Immunity

The antiviral innate immunity is the first line of host defense against viral infection. Mitochondrial antiviral signaling protein (MAVS, also named Cardif/IPS-1/VISA) is a critical protein in RNA virus-induced antiviral signaling pathways. Our previous research suggested that E3 ubiquitin-protein ligases RING-finger protein (RNF90) negatively regulate cellular antiviral responses by targeting STING for degradation, though its role in RNA virus infection remains unknown. This study demonstrated that RNF90 negatively regulated RNA virus-triggered antiviral innate immune responses in RNF90-silenced PMA-THP1 cells, RNF90-deficient cells (including HaCaTs, MEFs, and BMDMs), and RNF90-deficient mice. However, RNF90 regulated RNA virus-triggered antiviral innate immune responses independent of STING. RNF90 promoted K48-linked ubiquitination of MAVS and its proteasome-dependent degradation, leading to the inhibition of innate immune responses. Altogether, our findings suggested a novel function and mechanism of RNF90 in antiviral innate immunity.

scholarly journals Virus Caused Imbalance of Type I IFN Responses and Inflammation in COVID-19

2021 ◽  
Vol 12 ◽  
Author(s):  
Jintao Zhang ◽  
Chunyuan Zhao ◽  
Wei Zhao
Keyword(s):  
Innate Immunity ◽  
Innate Immune System ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Type I Ifn ◽  
Antiviral Responses ◽  
Public Health Challenges ◽  
Host Innate Immunity ◽  
Efficient Elimination

The global expansion of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged as one of the greatest public health challenges and imposes a great threat to human health. Innate immunity plays vital roles in eliminating viruses through initiating type I interferons (IFNs)-dependent antiviral responses and inducing inflammation. Therefore, optimal activation of innate immunity and balanced type I IFN responses and inflammation are beneficial for efficient elimination of invading viruses. However, SARS-CoV-2 manipulates the host’s innate immune system by multiple mechanisms, leading to aberrant type I IFN responses and excessive inflammation. In this review, we will emphasize the recent advances in the understanding of the crosstalk between host innate immunity and SARS-CoV-2 to explain the imbalance between inflammation and type I IFN responses caused by viral infection, and explore potential therapeutic targets for COVID-19.

scholarly journals Extensive evolutionary and functional diversity among mammalian AIM2-like receptors

2012 ◽  
Vol 209 (11) ◽  
pp. 1969-1983 ◽  
Author(s):  
Rebecca L. Brunette ◽  
Janet M. Young ◽  
Deborah G. Whitley ◽  
Igor E. Brodsky ◽  
Harmit S. Malik ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Phylogenetic Analysis ◽  
Gene Family ◽  
Functional Diversity ◽  
Innate Immune ◽  
Type I Interferons ◽  
Type I ◽  
Antiviral Responses ◽  
Immune Detection ◽  
Dependent Type

Innate immune detection of nucleic acids is important for initiation of antiviral responses. Detection of intracellular DNA activates STING-dependent type I interferons (IFNs) and the ASC-dependent inflammasome. Certain members of the AIM2-like receptor (ALR) gene family contribute to each of these pathways, but most ALRs remain uncharacterized. Here, we identify five novel murine ALRs and perform a phylogenetic analysis of mammalian ALRs, revealing a remarkable diversification of these receptors among mammals. We characterize the expression, localization, and functions of the murine and human ALRs and identify novel activators of STING-dependent IFNs and the ASC-dependent inflammasome. These findings validate ALRs as key activators of the antiviral response and provide an evolutionary and functional framework for understanding their roles in innate immunity.

scholarly journals Reprogramming Interferon Regulatory Factor Signaling in Cardiometabolic Diseases

Physiology ◽  
2017 ◽  
Vol 32 (3) ◽  
pp. 210-223 ◽  
Author(s):  
Yaxing Zhang ◽  
Hongliang Li
Keyword(s):  
Innate Immunity ◽  
Immune Responses ◽  
Immune Cells ◽  
Interferon Regulatory Factor ◽  
Innate Immune ◽  
Innate Immune Responses ◽  
Regulatory Factor ◽  
Cardiometabolic Diseases ◽  
Evolutionarily Conserved

Interferon regulatory factors (IRFs) are evolutionarily conserved proteins expressed not only in immune cells but also in other tissues and organs outside the immune system. In this review, we discuss mechanisms responsible for IRF-mediated innate immune responses and the function and mechanism of IRFs in cardiometabolic diseases. We focus on the role of IRFs in innate immunity and cardiometabolic homeostasis, and highlight reprogrammed IRF signaling.

scholarly journals MAVS Coordination of Antiviral Innate Immunity

2015 ◽  
Vol 89 (14) ◽  
pp. 6974-6977 ◽  
Author(s):  
Christine Vazquez ◽  
Stacy M. Horner
Keyword(s):  
Immune Response ◽  
Innate Immunity ◽  
Endoplasmic Reticulum ◽  
Retinoic Acid ◽  
Rna Virus ◽  
Adaptor Protein ◽  
Innate Immune ◽  
Antiviral Signaling ◽  
Antiviral Innate Immunity ◽  
Inducible Gene

RNA virus infection is sensed in the cytoplasm by the retinoic acid-inducible gene I (RIG-I)-like receptors. These proteins signal through the host adaptor protein MAVS to trigger the antiviral innate immune response. Here, we describe how MAVS subcellular localization impacts its function and the regulation underlying MAVS signaling. We propose a model to describe how the coordination of MAVS functions at the interface between the mitochondria and the mitochondrion-associated endoplasmic reticulum (ER) membrane programs antiviral signaling.

scholarly journals Double-Stranded RNA Sensors and Modulators in Innate Immunity

2019 ◽  
Vol 37 (1) ◽  
pp. 349-375 ◽  
Author(s):  
Sun Hur
Keyword(s):  
Innate Immunity ◽  
Immune Defense ◽  
Innate Immune ◽  
Protein Kinase R ◽  
Double Stranded Rna ◽  
Adenosine Deaminases ◽  
Binding Domains ◽  
Dsrna Binding ◽  
Rna Sensors ◽  
Antiviral Innate Immunity

Detection of double-stranded RNAs (dsRNAs) is a central mechanism of innate immune defense in many organisms. We here discuss several families of dsRNA-binding proteins involved in mammalian antiviral innate immunity. These include RIG-I-like receptors, protein kinase R, oligoadenylate synthases, adenosine deaminases acting on RNA, RNA interference systems, and other proteins containing dsRNA-binding domains and helicase domains. Studies suggest that their functions are highly interdependent and that their interdependence could offer keys to understanding the complex regulatory mechanisms for cellular dsRNA homeostasis and antiviral immunity. This review aims to highlight their interconnectivity, as well as their commonalities and differences in their dsRNA recognition mechanisms.

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