In addition, these cells feature stable knockout of either the RIG-I (Retinoic Acid Inducible protein 1), MDA5 (Melanoma Differentiation Associated gene 5), or MAVS (Mitochondrial antiviral-signaling protein) genes. (invivogen.com)
Outer membrane2
Upon recognition of dsRNA, RIG-I and MDA5 are recruited by the MAVS adaptor to the outer membrane of the mitochondria leading to the activation of several transcription factors, including interferon regulatory factors (IRFs) and NF-κB [3]. (invivogen.com)
Here we describe human NLRX1, a highly conserved nucleotide-binding domain (NBD)- and leucine-rich-repeat (LRR)-containing family member (known as NLR) that localizes to the mitochondrial outer membrane and interacts with MAVS. (elsevierpure.com)
Protein5
Upon viral RNA recognition, antiviral signaling requires RIG-I redistribution from the cytosol to membranes where it binds the adaptor protein, MAVS. (duke.edu)
Here we identify the mitochondrial targeting chaperone protein, 14-3-3ε, as a RIG-I-binding partner and essential component of a translocation complex or 'translocon' containing RIG-I, 14-3-3ε, and the TRIM25 ubiquitin ligase. (duke.edu)
Innate immunity to viruses involves receptors such as RIG-I, which senses viral RNA and triggers an IFN-β signaling pathway involving the outer mitochondrial membrane protein MAVS. (nih.gov)
Economic Assistance: National Institutes of Well being (NIH U19AI066328, AI069285), University of Washington Pathobiology Instruction Grant (NIH 2T32AI007509).AbbreviationsHCV IFN NK PAMP PRR TLR3 RIG-I MAVS TRIF IRF Hepatitis C Virus Interferon Natural Killer Pathogen Connected Molecular Pattern Pattern Recognition Receptor Toll-like Receptor 3 Retinoic Acid Inducible Gene I Mitochondrial Antiviral- Cathepsin B site signaling protein TIR-domain-containing adapter-inducing IFN- Interferon Regulatory FactorJ Hepatol. (bet-bromodomain.com)
Recently, we reported that the nucleus-mitochondria positive feedback loop formed by p90 ribosomal S6 kinase (p90RSK) and phosphorylation of S496 on ERK5 (a unique member of the mitogen-activated protein kinase family that is not only a kinase but also a transcriptional co-activator) were vital signaling events that played crucial roles in linking mitochondrial dysfunction, nuclear telomere dysfunction, persistent SASP induction, and atherosclerosis. (oaepublish.com)
MDA54
2005 . IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. (invivogen.com)
TRIF for TLR3 and TLR4, and MAVS (for MDA5 and RIG-I) are activated. (cdc.gov)
In addition, NSP8 impaired IFN expression triggered by overexpression of the signaling molecules RIG-I, MDA5, and MAVS, instead of TBK1 and IRF3-5D, an active form of IRF3. (bvsalud.org)
From a mechanistic view, NSP8 interacts with RIG-I and MDA5, and thereby prevents the assembly of the RIG-I/MDA5-MAVS signalosome, resulting in the impaired phosphorylation and nuclear translocation of IRF3. (bvsalud.org)
Innate immune2
The RIG-I translocon directs RIG-I redistribution from the cytosol to membranes where it mediates MAVS-dependent innate immune signaling during acute RNA virus infection. (duke.edu)
Mitochondria are also platforms for antiviral signalling2 and, due to their bacterial origin, mtDNA and other mitochondrial components trigger innate immune responses and inflammatory pathology2,3. (regenerativemedicine.net)
Interacts1
Retinoic acid-inducible gene I (RIG-I) is a key pattern recognition receptor that senses viral RNA and interacts with the mitochondrial adaptor MAVS, triggering a signaling cascade that results in the production of type I interferons (IFNs). (psu.edu)
Viral infection2
Here we demonstrate for the first time that MAVS undergoes extensive tyrosinephosphorylation upon viral infection, indicating that MAVS phosphorylation might play an important role in MAVS function. (nih.gov)
The RIG-like helicase (RLH) family of intracellular receptors detect viral nucleic acid and signal through the mitochondrial antiviral signalling adaptor MAVS (also known as Cardif, VISA and IPS-1) during a viral infection. (elsevierpure.com)
Downstream1
These experiments identify a novel residue of MAVS that is crucially involved in the recruitment of TRAF3/TRAF6 and in downstream propagation of MAVS signaling. (nih.gov)
Proteins1
The mammalian genome comprises nuclear DNA (nDNA) derived from both parents and mitochondrial DNA (mtDNA) that is maternally inherited and encodes essential proteins required for oxidative phosphorylation. (regenerativemedicine.net)
Promotes2
The adaptor MAVS promotes NLRP3 mitochondrial localization and inflammasome activation. (isbscience.org)
This signaling axis is initiated by K63-linked ubiquitination of RIG-I mediated by the E3 ubiquitin ligase TRIM25, which promotes the interaction of RIG-I with MAVS. (psu.edu)
Interferon2
Belgnaoui SM, Paz S, Hiscott J. Orchestrating the interferon antiviral response through the mitochondrial antiviral signaling (MAVS) adapter. (journal-jmsr.net)
Expression of NLRX1 results in the potent inhibition of RLH- and MAVS-mediated interferon-β promoter activity and in the disruption of virus-induced RLH-MAVS interactions. (elsevierpure.com)
Cytosolic1
Our publication in PLoS Pathogens (2014) demonstrated that infection of conventional DCs with MVA, leads to the induction of type I IFN production that is dependent on the cytosolic DNA sensor cGAS (cyclic GMP-AMP synthase) and its adaptor STING (stimulator of IFN genes). (mskcc.org)
A tyrosine-scanning mutational analysis revealed that MAVS tyrosine-9 (Y9) is a phosphorylation site that is required for IFN-β signaling. (nih.gov)
Indeed, MAVS Y9F mutation severely impaired TRAF3/TRAF6 recruitment and displayed decreased tyrosinephosphorylation in response to VSV infection compared to wild type MAVS. (nih.gov)
Functionally, MAVS Y9 phosphorylation contributed to MAVS antiviral function without interfering with its apoptosis property. (nih.gov)
Further mechanistic study has shown that the mitochondrial oxidative phosphorylation (OXPHOS), membrane potential, and ATP production were significantly decreased two days after the overexpression of S and ORF-9B subunits, while S subunits induced higher level of reactive oxygen species (ROS). (bvsalud.org)
Dysfunction2
One of the underlying mechanisms of long COVID may be mitochondrial dysfunction. (mdpi.com)
Telomeric DNA damage-induced mitochondrial dysfunction and increased reactive oxygen species production are hallmarks of premature senescence. (oaepublish.com)
Gene1
Finally, CRISPR-Cas9 gene targeting in human keratinocytes showed that the TRIM25-RIG-I-MAVS triad is important for eliciting an antiviral immune response to HPV16 infection. (psu.edu)
Publication1
Scholars@Duke publication: The mitochondrial targeting chaperone 14-3-3ε regulates a RIG-I translocon that mediates membrane association and innate antiviral immunity. (duke.edu)
Our results further showed that E6 inhibited the TRIM25- mediated K63-linked ubiquitination of RIG-I and its CARD-dependent interaction with MAVS. (psu.edu)
Vital1
Although MAVS is vital to antiviral immunity, its regulation from within the mitochondria remains unknown. (elsevierpure.com)
Antiviral11
Herein, we report the identification of a novel protein termed MAVS (mitochondrial antiviral signaling), which mediates the activation of NF-kappaB and IRF 3 in response to viral infection. (nih.gov)
Conversely, overexpression of MAVS induces the expression of IFN-beta through activation of NF-kappaB and IRF 3, thus boosting antiviral immunity. (nih.gov)
Additionally, the target association between miR-3470b and mitochondrial antiviral signaling protein (MAVS) was predicted by target gene prediction tools and further validated using a dual-luciferase reporter assay, and the expression of MAVS mRNA and protein levels was negatively associated with miR-3470b levels. (biomedcentral.com)
Our findings is the first to reveal that miR-3470b as a novel host factor regulates BEFV replication via directly targeting the MAVS gene in BHK-21 cells and may provide a potential strategy for developing effective antiviral therapy. (biomedcentral.com)
Through a combination of proteomic, metabolomic, transcriptomic, and perturbation studies, we found that sphingolipid metabolism in astrocytes triggers the interaction of the C2 domain in cytosolic phospholipase A2 (cPLA2) with the CARD domain in mitochondrial antiviral signaling protein (MAVS), boosting NF-κB-driven transcriptional programs that promote CNS inflammation in experimental autoimmune encephalomyelitis (EAE) and, potentially, multiple sclerosis. (nih.gov)
Once activated, RIG-I and MDA5 induce dimerization of a protein called MAVS (Mitochondrial Antiviral-Signaling Protein). (ebiohippo.com)
MAVS interacts with RIG-I via TRAF, resulting in the induction of antiviral and inflammatory responses including NF-kB and IRF signaling pathways. (ecologicalsgardens.com)
The PB2 subunit of the influenza virus RNA polymerase affects virulence by interacting with the mitochondrial antiviral signaling protein and inhibiting expression of beta interferon. (ox.ac.uk)
Here, we demonstrate that the PB2 protein interacts with the mitochondrial antiviral signaling protein, MAVS (also known as IPS-1, VISA, or Cardif), and inhibits MAVS-mediated beta interferon (IFN-beta) expression. (ox.ac.uk)
Overall this study implicates the PB2 protein in the regulation of host antiviral innate immune pathways and suggests an important role for the mitochondrial association of the PB2 protein in determining virulence. (ox.ac.uk)
Furthermore, we found that the 3CD protein interacted with the N-terminal structural domain of RIG-I protein, interfered with the interaction between RIG-I and MAVS, and degraded RIG-I protein through the proteasomal degradation pathway, thereby inhibiting its mediated antiviral innate immunity to promote DHAV-1 replication. (biomedcentral.com)
Induces1
For viral RNA sensing, RLR induces polymerization of MAVS and promotes binding of TRAF2 , TRAF5 , and TRAF6 . (ebiohippo.com)
Overexpression1
Moreover, the overexpression of MAVS or silencing of miR-3470b by its inhibitors suppressed BEFV replication, and knockdown of MAVS by small interfering RNA also promoted the replication of BEFV. (biomedcentral.com)
Recruitment2
cPLA2 recruitment to MAVS also disrupts MAVS-hexokinase 2 (HK2) interactions, decreasing HK enzymatic activity and the production of lactate involved in the metabolic support of neurons. (nih.gov)
In addition, enterovirus 71 (EV71) inhibits the formation of a complex between RIG-1 and MAVS by interacting with the CARD at the N-terminus of RIG-I, thereby blocking MAVS recruitment and subsequent nuclear translocation of IRF3 [ 17 ]. (biomedcentral.com)
TLR41
The glycoprotein, Fetuin-A acts as an adaptor between saturated FFAs and TLR4. (ecologicalsgardens.com)
Regulates2
17. SIRT5 regulates the mitochondrial lysine succinylome and metabolic networks. (nih.gov)
Deubiquitination of OTUB1 /2 (Ubiquitin thioesterase) regulates ubiquitination of TRAF2 /5/6 and is required for association with MAVS. (ebiohippo.com)
Regulation1
7. SIRT5-Related Desuccinylation Modification Contributes to Quercetin-Induced Protection against Heart Failure and High-Glucose-Prompted Cardiomyocytes Injured through Regulation of Mitochondrial Quality Surveillance. (nih.gov)
Viral2
Silencing of MAVS expression through RNA interference abolishes the activation of NF-kappaB and IRF 3 by viruses, thereby permitting viral replication. (nih.gov)
Open in a separate window Figure.1 Innate immune signaling by PRRsCytosolic viral RNA is recognized by the RIG I-like receptors that activate MAVS. (ecologicalsgardens.com)
Targets2
The transmembrane domain targets MAVS to the mitochondria, implicating a new role of mitochondria in innate immunity. (nih.gov)
Collectively, these findings define a novel immunometabolic mechanism that drives pro-inflammatory astrocyte activities, outlines a new role for MAVS in CNS inflammation, and identifies candidate targets for therapeutic intervention. (nih.gov)
Activity1
Metabolic Control of Astrocyte Pathogenic Activity via cPLA2-MAVS. (nih.gov)
Domain1
MAVS contains an N-terminal CARD-like domain and a C-terminal transmembrane domain, both of which are essential for MAVS signaling. (nih.gov)