Orchestrating the interferon antiviral response through the mitochondrial antiviral signaling (MAVS) adapter

Belgnaoui, S. Mehdi; Paz, Suzanne; Hiscott, John

doi:10.1016/j.coi.2011.08.001

Cited by 201 publications

(189 citation statements)

References 54 publications

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“…Recently it has been reported that some membrane proteins including IPS-1 and STING play a key role for adequate control of innate immune signaling [2,[16][17][18]]. …”

Section: Discussionmentioning

confidence: 99%

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TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

Kondo

Watanabe

Hatakeyama

2012

Biochemical and Biophysical Research Communications

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Innate immune responses are triggered by pathogen-associated molecular patterns (PAMPs) through pattern recognition receptors (PRRs) and then activate intracellular signaling pathways including NF-B and interferon regulatory factors. Recently, it has been reported that tripartite motif (TRIM) proteins function as crucial regulators via ubiquitin-mediated modifications for these signaling pathways. In this study, we showed that one of the TRIM family ubiquitin ligases, TRIM59, interacts with ECSIT as an adaptor protein required for the TLR-mediated transduction pathway. Luciferase reporter assays using reporter plasmids including NF-B responsive element, interferon (IFN-) promoter and interferon-sensitive response element (ISRE) showed that overexpression of TRIM59 repressed their transcriptional activities, whereas knockdown of TRIM59 enhanced their transcriptional activities. Furthermore, TRIM59 inhibited phosphorylation and dimerization of IRF3 and IRF7, suggesting that TRIM59 negatively regulates upstream kinases for IRFs. These findings indicate that TRIM59 may serve as a multifunctional regulator for innate immune signaling pathways.3

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“…Recently it has been reported that some membrane proteins including IPS-1 and STING play a key role for adequate control of innate immune signaling [2,[16][17][18]]. …”

Section: Discussionmentioning

confidence: 99%

“…RIG-I-like receptors (RLRs), such as RIG-I and MDA5, recognize viral RNA and transmit signals to the downstream mitochondrion-located adaptor protein IPS-1 (also known as MAVS, VISA, and Cardif) [2]. IPS-1 then activates IKK-protein-kinase family members.…”

Section: Introductionmentioning

confidence: 99%

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

Kondo

Watanabe

Hatakeyama

2012

Biochemical and Biophysical Research Communications

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“…Both RIG-I and MDA5 contain two Nterminal caspase recruiting domains (CARDs), a central ASP-Glu-xAsp/His (DExD/H)-box RNA helicase domain (HD) and a C-terminal regulatory domain (RD) [2,3]. In general, RIG-I preferentially binds to a short, uncapped 5 0 -trihosphorylated (5 0 -ppp) ssRNA juxtaposed to a short region of dsRNA [4,5], whereas MDA5 recognizes the internal duplex structure of dsRNA [6].…”

Section: Introductionmentioning

confidence: 99%

“…However, both are initially characterized as dsRNA-binding proteins that respond to poly (I:C), a synthetic form of dsRNA and actually, they prefer to different-sized poly (I:C) [7,8]. Following recognition of such ligands, RIG-I and MDA5 are activated and interact with a mitochondrial antiviral signaling protein (MAVS, also known as IPS-1/ VISA/Cardif), to transit antiviral signaling to downstream signaling molecules (such as TBK1 and IRF3/7) and finally orchestrate the IFN antiviral response [2,3,9].…”

Section: Introductionmentioning

confidence: 99%

“…Structurally, MAVS harbors a N-terminal CARD domain that mainly mediates interaction with the CARD domain of the activated RIG-I and MDA5, a central proline-rich domain involved in interaction with various downstream targets, and a C-terminal transmembrane domain (TM) that is required for MAVS translocation into the outer mitochondrial membrane [3]. The mitochondrial localization of MAVS makes it to be a central adapter protein for recruiting and activating downstream signaling molecules, such as TBK1 and IRF3/7, the latter of which subsequently translocate into the nucleus turning on the transcription of IFN [10e14].…”

Section: Introductionmentioning

confidence: 99%

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Fish MAVS is involved in RLR pathway-mediated IFN response

Zhang

et al. 2014

Fish & Shellfish Immunology

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Post‐translational regulation of antiviral innate signaling

et al. 2017

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The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required. Posttranslational modifications (PTMs), such as the covalent linkage of functional groups to amino acid chains, are crucial for this immune homeostasis in antiviral responses. Canonical PTMs including phosphorylation and ubiquitination have been extensively studied and other PTMs such as methylation, acetylation, SUMOylation, ADP-ribosylation and glutamylation are being increasingly implicated in antiviral innate immunity. Here we summarize our recent understanding of the most important PTMs regulating the antiviral innate immune response, and their role in virus-related immune pathogenesis.Keywords: Antiviral immunity r Interferons r Phosphorylation r Post-translational modifications r PRR r Ubiquitination IntroductionInfectious diseases, especially virus infections, are still a serious threat to humanity and the host innate immune system represents a critical defense against invading viruses. Host cells can initiate these innate immune responses by detecting viral DNA and RNA with a set of pattern recognition receptors (PRRs) including the toll-like receptor (TLR) family and the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, as well as cytosolic DNA sensors such as cyclic GMP-AMP (cGAMP) synthase (cGAS), IFI16 and DDX41 [1,2]. After recognition of viral nucleic acids, these PRRs trigger the production of proinflammatory cytokines, chemokines and type I interferons (IFNs), which subsequently induce synthesis of antiviral proteins, death of infected cells and activation of the adaptive immune response [3,4]. These antiviral signals Correspondence: Dr. Baoxue Ge e-mail: gebaoxue@sibs.ac.cn must be spatially and temporally orchestrated to achieve an optimal outcome for the host and much attention has been raised to understanding the signaling pathways and regulatory factors in the antiviral innate immunity.Toll-like receptors, including TLR3, TLR7, TLR8 and TLR9, sense endosomal nucleic acids derived from the enclosed microbes and infected apoptotic cells. While TLR9 detects unmethylated CpG DNA species, TLR3 and TLR7/8 recognize double-stranded RNA (dsRNA) and single-stranded RNA (ssRNA), respectively [5] ( Fig. 1). Following ligand binding, the TLRs form a signaling platform in which distinct Toll/interleukin-1 receptor (TIR) domaincontaining adaptors are engaged. For instance, TLR3 signals via TIR-domain-containing adaptor protein inducing interferon beta (TRIF), and TLR7/8/9 rel...

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Orchestrating the interferon antiviral response through the mitochondrial antiviral signaling (MAVS) adapter

Cited by 201 publications

References 54 publications

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

TRIM59 interacts with ECSIT and negatively regulates NF-κB and IRF-3/7-mediated signal pathways

Fish MAVS is involved in RLR pathway-mediated IFN response

Post‐translational regulation of antiviral innate signaling

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