Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5

Brisse, Morgan; Ly, Hinh

doi:10.3389/fimmu.2019.01586

Cited by 285 publications

(282 citation statements)

References 395 publications

(491 reference statements)

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“…When poly (I:C) is administered, the innate defence system acts as if challenged by a viral pathogen and initiates molecular mechanisms designed to fight the aetiological agent. Poly (I:C) effects its antiviral properties by a broadly expressed, well-conserved, toll-like receptor 3 (tlr3) (Kitao et al, 2009;Tanekhy, 2016;Zhou et al, 2014); retinoic acid-inducible gene I (rig-1) and melanoma differentiation-associated protein 5 (Mda5), both termed RIG-I-like receptors (RLRs); and class A scavenger receptors (SR-As) (Brisse & Ly, 2019;Semple et al, 2018;Zhou et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

Metabolic and immune responses of Chinook salmon (Oncorhynchus tshawytscha) smolts to a short‐term poly (I:C) challenge

Lulijwa

Mérien

Burdass

et al. 2020

Journal of Fish Biology

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Polyinosinic:polycytidylic acid [poly (I:C)] was administered in vivo to Chinook salmon (Oncorhynchus tshawytscha) post‐smolts to determine the immune responses on haematological and cellular functional parameters, including spleen (SP), head kidney (HK) and red blood cell (RBC) cytokine expression, as well as serum metabolomics. Poly (I:C) in vivo (24 h exposure) did not affect fish haematological parameters, leucocyte phagocytic activity and phagocytic index, reactive oxygen species and nitric oxide production. Gas chromatography–mass spectrometry–based metabolomics revealed that poly (I:C) significantly altered the serum biochemistry profile of 25 metabolites. Metabolites involved in the branched‐chain amino acid/glutathione and transsulphuration pathways and phospholipid metabolism accumulated in poly (I:C)–treated fish, whereas those involved in the glycolytic and energy metabolism pathways were downregulated. At cytokine transcript level, poly (I:C) induced a significant upregulation of antiviral ifnγ in HK and Mx1 protein in HK, SP and RBCs. This study provides evidence for poly (I:C)–induced, immune‐related biomarkers at metabolic and molecular levels in farmed O. tshawytscha in vivo. These findings provide insights into short‐term effects of poly (I:C) at haematological, innate and adaptive immunity and metabolic levels, setting the stage for future studies.

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Section: Introductionmentioning

confidence: 99%

Metabolic and immune responses of Chinook salmon (Oncorhynchus tshawytscha) smolts to a short‐term poly (I:C) challenge

Lulijwa

Mérien

Burdass

et al. 2020

Journal of Fish Biology

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“…3). Ubiquitylation events are reversible processes, and, accordingly, several deubiquitylating enzymes, in particular ubiquitin specific peptidase 3 (USP3), USP21 and CYLD lysine 63 deubiquitinase (CYLD), modulate RIG-I signalling by removing K63-polyubiquitin chains, although with unique kinetics (reviewed elsewhere 112,118 ). On the other hand, USP4 and USP15 enhance the stability of RIG-I and TRIM25, respectively, by proteolytically cleaving K48-linked ubiquitylation from these molecules 119,120 .…”

Section: Single-nucleotide Polymorphismsmentioning

confidence: 99%

RIG-I-like receptors: their regulation and roles in RNA sensing

2020

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| Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) are key sensors of virus infection, mediating the transcriptional induction of type I interferons and other genes that collectively establish an antiviral host response. Recent studies have revealed that both viral and host-derived RNAs can trigger RLR activation; this can lead to an effective antiviral response but also immunopathology if RLR activities are uncontrolled. In this Review , we discuss recent advances in our understanding of the types of RNA sensed by RLRs in the contexts of viral infection, malignancies and autoimmune diseases. We further describe how the activity of RLRs is controlled by host regulatory mechanisms, including RLR-interacting proteins, post-translational modifications and non-coding RNAs. Finally , we discuss key outstanding questions in the RLR field, including how our knowledge of RLR biology could be translated into new therapeutics.

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“…Although RIG-I and MDA5 share certain sequence, structural and functional similarities, they have distinct structural and functional properties and are regulated by distinct post-translational modifications [13]. For example, RIG-I but not MDA5 exhibits an auto-inhibition state through the intramolecular interaction of its CARDs and the C-terminal tail domain (CTD) in un-infected cells [14].…”

Section: Author Summarymentioning

confidence: 99%

“…The RLRs then form longer filaments on viral RNA and then interact with the mitochondrial adaptor protein VISA (also called MAVS, IPS-1, and Cardif) through their respective N-terminal caspase activation and recruitment domains (CARDs) [7][8][9][10][11][12]. VISA acts as a central platform for assembly of a virus-induced complex that activates TAK1-IKK and TBK1/IKKε kinases, leading to activation of the transcription factors NF-κB and IRF3 and ultimate induction of downstream antiviral genes [11].Although RIG-I and MDA5 share certain sequence, structural and functional similarities, they have distinct structural and functional properties and are regulated by distinct post-translational modifications [13]. For example, RIG-I but not MDA5 exhibits an auto-inhibition state through the intramolecular interaction of its CARDs and the C-terminal tail domain (CTD) in un-infected cells [14].…”

mentioning

confidence: 99%

ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response

Zhong

Zang

et al. 2020

PLoS Pathog

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The retinoic acid-inducible gene-I (RIG-I)-like receptors (RLRs), including RIG-I and melanoma differentiation-associated gene 5 (MDA5), sense cytoplasmic viral RNA and initiate innate antiviral responses. How RIG-I and MDA5 are differentially regulated remains enigmatic. In this study, we identified the guanylate-binding protein (GBP) and zinc-finger FYVE domain-containing protein ZFYVE1 as a negative regulator of MDA5-but not RIG-I-mediated innate antiviral responses. ZFYVE1-deficiency promoted MDA5-but not RIG-I-mediated transcription of downstream antiviral genes. Comparing to wild-type mice, Zfyve1 -/mice were significantly protected from lethality induced by encephalomyocarditis virus (EMCV) that is sensed by MDA5, whereas Zfyve1 -/and Zfyve1 +/+ mice were comparable to death induced by vesicular stomatitis virus (VSV) that is sensed by RIG-I. Mechanistically, ZFYVE1 interacted with MDA5 but not RIG-I. ZFYVE1 bound to viral RNA and decreased the ligand binding and oligomerization of MDA5. These findings suggest that ZFYVE1 acts as a specific negative regulator of MDA5-mediated innate immune responses by inhibiting its ligand binding and oligomerization. Author summaryRIG-I and MDA5 are the main cytosolic sensors for invaded viral RNA. How these sensors are differentially regulated is largely unknown. In this study, we identified ZFYVE1 as a specific regulator of MDA5-but not RIG-I-mediated antiviral responses. ZFYVE1deficiency promotes antiviral immune responses and renders the mice less susceptible to EMCV-induced death. ZFYVE1 interacts with MDA5 and viral dsRNA, and inhibits the ligand binding and oligomerization of MDA5. Our study reveals a negative regulatory mechanism for keeping MDA5 inactive in un-infected cells, which contributes to our understanding on how innate antiviral responses are delicately regulated to avoid immune damage. ) to H. B.S, Q.Y., and C.L. The funders had no role in study patterns (PAMPs) are sensed by pathogen recognition receptors (PRRs). The PRRs then trigger a series of signaling events, leading to the induction of type I interferons (IFNs), proinflammatory cytokines and other downstream antiviral effector proteins. These effectors act to inhibit viral replication, clear the infected cells and facilitate adaptive immune responses [1].During viral infection, viral nucleic acids act as important PAMPs. It has been demonstrated that the membrane-associated Toll-like receptor 3 (TLR3) recognizes extracellular and endosomal viral RNA, whereas the cytosolic viral RNA is detected by retinoic acid-inducible gene-I (RIG-I) like receptors (RLRs), including RIG-I and melanoma differentiation-associated gene 5 (MDA5) [2]. Upon binding to their ligands, RIG-I and MDA5 undergo conformational changes and recruit PP1α/γ for their dephosphorylation, which is followed by their K63-linked polyubiquitination by several E3 ubiquitin ligases [3][4][5][6][7]. The RLRs then form longer filaments on viral RNA and then interact with the mitochondrial adaptor protein VISA (also called MAVS, IPS-1, and...

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Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5

Cited by 285 publications

References 395 publications

Metabolic and immune responses of Chinook salmon (Oncorhynchus tshawytscha) smolts to a short‐term poly (I:C) challenge

Metabolic and immune responses of Chinook salmon (Oncorhynchus tshawytscha) smolts to a short‐term poly (I:C) challenge

RIG-I-like receptors: their regulation and roles in RNA sensing

ZFYVE1 negatively regulates MDA5- but not RIG-I-mediated innate antiviral response

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