Affinage

MAVS

Mitochondrial antiviral-signaling protein · UniProt Q7Z434

Length
540 aa
Mass
56.5 kDa
Annotated
2026-04-28
100 papers in source corpus 48 papers cited in narrative 49 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAVS is a mitochondrial outer membrane adaptor protein that serves as the central signaling hub in the RIG-I-like receptor (RLR) antiviral innate immune pathway, transducing viral RNA detection into type I/III interferon production, NF-κB activation, apoptosis, inflammasome activation, and autophagy. Upon viral RNA sensing, RIG-I and MDA5 engage the N-terminal CARD domain of MAVS, which—together with K63-linked polyubiquitin chains synthesized by TRIM31/Riplet/Ube2N—catalyzes conversion of MAVS into prion-like functional aggregates on mitochondria; these aggregates are stabilized by palmitoylation (ZDHHC7 at Cys508, ZDHHC24, CPT1A-recruited ZDHHC4 at Cys79) and poly-SUMOylation (PIAS3), which promotes MAVS phase separation and IRF3 recruitment via SUMO-SIM interactions (PMID:21782231, PMID:39141356, PMID:37188808, PMID:38016475). Aggregated MAVS recruits TRAF2/3/5/6 through conserved TRAF-interaction motifs, enabling TBK1/IKKε-mediated phosphorylation of MAVS serine/threonine clusters that directly bind and recruit IRF3 for activation, while TRAF-dependent ubiquitin chains engage NEMO to activate NF-κB (PMID:25636800, PMID:29125880, PMID:16858409). MAVS activity is tightly regulated by negative feedback through K48-linked ubiquitination (RNF115, Smurf2, TRIM28, MARCH5), arginine methylation by PRMT7 (R52) and PRMT9 (R41/R43) that suppress aggregation in resting cells, phosphorylation-induced degradation by NLK, caspase-3 cleavage, and autophagy via LC3 binding to a LIR motif; beyond canonical antiviral signaling, MAVS also activates MKK7-JNK2-dependent apoptosis, scaffolds NLRP3 inflammasome assembly, stabilizes p53 by blocking MDM2, and compartmentalizes metabolic flux through organelle-specific interactions with G6PD and GFPT (PMID:34171297, PMID:36028484, PMID:31324787, PMID:30878284, PMID:24651600, PMID:24048902, PMID:31968249, PMID:37660168).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 2005 High

    The discovery of MAVS as the missing adaptor linking cytoplasmic RNA sensors RIG-I/MDA5 to IRF3 and NF-κB activation resolved how the cell transduces viral RNA detection into interferon production, establishing that the mitochondrial outer membrane is a signaling platform for innate immunity.

    Evidence RNAi knockdown, overexpression, epistasis experiments, domain mutagenesis, co-immunoprecipitation across four independent groups (MAVS/IPS-1/VISA/Cardif)

    PMID:16125763 PMID:16127453 PMID:16153868

    Open questions at the time
    • Mechanism of MAVS activation upon RIG-I binding unknown
    • How mitochondrial localization contributes beyond membrane anchoring unclear
    • Downstream effector recruitment mechanism unresolved
  2. 2006 High

    Identification of TRAF3 as a direct MAVS partner via a conserved TRAF-interaction motif established the molecular basis for how MAVS couples to the TBK1-IRF3 kinase cascade for type I IFN induction.

    Evidence Direct binding assays, TRAF domain mutagenesis, co-immunoprecipitation, siRNA knockdown

    PMID:16858409

    Open questions at the time
    • Which other TRAFs contribute remained unclear
    • How MAVS activates NF-κB branch separately from IRF3 not resolved
    • No structural model of MAVS-TRAF complex
  3. 2008 High

    Crystal structure of the MAVS CARD domain revealed the six-helix bundle architecture underlying homotypic CARD-CARD interactions with RIG-I, and identification of splice variants showed MAVS can differentially activate IRF3 versus NF-κB.

    Evidence X-ray crystallography at 2.1 Å; cDNA cloning and functional reporter assays for splice variants

    PMID:18207245 PMID:18307765

    Open questions at the time
    • Full-length MAVS structure unavailable
    • Structural basis for selectivity of splice variant signaling unknown
    • CARD-CARD interaction interface with RIG-I not resolved
  4. 2011 High

    The discovery that MAVS forms prion-like aggregates on mitochondria—catalyzed by RIG-I in the presence of K63-linked polyubiquitin chains—fundamentally changed the signaling model from a simple receptor-adaptor interaction to an autocatalytic amplification mechanism.

    Evidence SDD-AGE, recombinant MAVS fibril reconstitution, in vitro IRF3 activation assay

    PMID:21782231

    Open questions at the time
    • Source of the K63-ubiquitin chains during physiological activation not identified
    • Structure of MAVS filaments unresolved
    • How aggregation is reversed/terminated unknown
  5. 2009 High

    Demonstration that MAVS induces caspase-dependent apoptosis independent of IFN production, and later identification of the MAVS-MKK7-JNK2 pathway, established MAVS as a bifunctional signaling hub for both innate immunity and programmed cell death.

    Evidence MAVS KO fibroblasts, Jnk1/2/Mkk7 KO mice, domain mapping, viral challenge

    PMID:19404494 PMID:24651600

    Open questions at the time
    • Relative contribution of apoptosis versus IFN in antiviral defense not quantified
    • Whether apoptotic and IFN pathways are activated simultaneously or sequentially unclear
  6. 2013 High

    MAVS was shown to scaffold NLRP3 inflammasome oligomerization in a transmembrane-domain-dependent manner, extending its role beyond interferon signaling to IL-1β-mediated inflammatory responses.

    Evidence Co-immunoprecipitation, MAVS-ΔTM mutant, MAVS knockdown in THP-1 macrophages, Sendai virus infection

    PMID:24048902

    Open questions at the time
    • Direct binding interface between MAVS and NLRP3 not mapped
    • Whether MAVS aggregation is required for inflammasome activation unknown
  7. 2015 High

    Identification of IKK/TBK1-phosphorylated serine/threonine clusters on MAVS that directly recruit IRF3 via a phospho-dependent interaction resolved how the MAVS signalosome specifically activates its key transcription factor substrate.

    Evidence In vitro kinase assays, phosphorylation site mutagenesis, phospho-MAVS pulldown with IRF3, structural analysis

    PMID:25636800

    Open questions at the time
    • Complete set of phosphorylation sites on MAVS not catalogued
    • Kinetics of phosphorylation relative to aggregation unclear
  8. 2017 High

    Quadruple TRAF2/3/5/6 knockout cells completely lost RNA virus responses, demonstrating that MAVS-TRAF interactions are non-redundantly essential and that TRAFs bridge MAVS to both TBK1/IKKε (via coiled-coil/SDD domain contacts) and NEMO (via ubiquitin chains).

    Evidence Multiple TRAF KO cell lines, ubiquitination assays, domain interaction mapping

    PMID:29125880

    Open questions at the time
    • Relative contributions of individual TRAFs to IFN versus NF-κB branches not fully dissected
    • Structural basis of TRAF-TBK1 interaction not determined
  9. 2019 High

    Discovery that NLK phosphorylates MAVS to trigger its degradation and that caspase-3 cleaves MAVS to prevent cytokine overproduction established key negative regulatory circuits operating at the level of MAVS protein turnover.

    Evidence NLK KO mice, kinase assay with site mutagenesis; Casp3 KO mice and cells, in vitro cleavage assays

    PMID:30878284 PMID:31324787

    Open questions at the time
    • Temporal ordering of different negative regulatory modifications during infection unclear
    • Whether NLK and caspase-3 act in the same or parallel pathways not tested
  10. 2019 Medium

    MAVS was found to interact with metabolic enzymes cPLA2, HK2, G6PD, and GFPT in an organelle-specific manner, linking innate immune signaling to metabolic reprogramming including pentose phosphate pathway flux and hexosamine biosynthesis.

    Evidence Proteomic/metabolomic analysis, co-immunoprecipitation, MAVS KO, glucose metabolic tracing, EAE model

    PMID:31813625 PMID:37660168

    Open questions at the time
    • Structural basis for organelle-specific metabolic interactions not determined
    • Whether metabolic reprogramming is required for or consequent to immune signaling unclear
    • In vivo relevance of each individual metabolic interaction not independently validated
  11. 2020 High

    Identification of constitutive K48-linked ubiquitination of MAVS by RNF115 in uninfected cells, along with roles for Smurf2, MARCH5, and TRIM28, revealed that basal MAVS levels are kept low through multiple E3 ligase-dependent degradation pathways to prevent spontaneous activation.

    Evidence Rnf115 KO mice with elevated MAVS protein; ubiquitination assays with site-specific mutagenesis for each E3

    PMID:24729608 PMID:31881323 PMID:33139700 PMID:37119745

    Open questions at the time
    • Relative contribution and hierarchy of different E3 ligases in homeostatic MAVS regulation not established
    • Whether these ligases are redundant or context-specific unclear
  12. 2021 High

    PRMT7-mediated monomethylation at R52 and PRMT9-mediated methylation at R41/R43 were shown to suppress MAVS aggregation in resting cells by blocking interactions with TRIM31 and RIG-I, establishing arginine methylation as a tonic inhibitory mechanism relieved upon infection.

    Evidence In vitro methyltransferase assays, R52A/R41A/R43A mutagenesis, Prmt7 KO mice, PRMT9 KO cells

    PMID:34171297 PMID:36028484

    Open questions at the time
    • Whether both PRMTs modify MAVS simultaneously or in distinct contexts not resolved
    • Methylation erasers for MAVS not identified
  13. 2023 High

    PIAS3-induced poly-SUMOylation was found to drive MAVS phase separation via SUMO-SIM interactions, with IRF3 recruited into MAVS droplets through its own SIM and released upon TBK1-mediated phosphorylation—providing a biophysical mechanism for signal amplification and transcription factor activation within the MAVS signalosome.

    Evidence SUMOylation assays, phase separation reconstitution, SIM mutagenesis, IRF3 phosphorylation-dependent release assay, SENP1 KO

    PMID:37188808

    Open questions at the time
    • Relationship between prion-like aggregation and liquid-liquid phase separation not clarified
    • In vivo phase separation of endogenous MAVS not demonstrated
  14. 2023 High

    Identification of unanchored K63-linked polyubiquitin chains on MAVS—synthesized by Ube2N/Riplet/TRIM31 and removed by USP10—as the direct RIG-I recruitment signal resolved the molecular trigger for MAVS prion-like conversion.

    Evidence Ube2N/USP10 KO, RIG-I CARD binding assays, MAVS aggregation by SDD-AGE

    PMID:37582970

    Open questions at the time
    • Whether unanchored chains arise before or after initial RIG-I-MAVS contact unclear
    • Stoichiometry of ubiquitin chain requirement not determined
  15. 2023 High

    Discovery that palmitoylation by ZDHHC4 (Cys79), ZDHHC7 (Cys508), and ZDHHC24 stabilizes MAVS aggregates and shifts ubiquitin modification from K48- to K63-linked chains established lipid modification as a critical activating switch for MAVS signaling.

    Evidence Acyl-RAC palmitoylation assays, site-specific Cys mutagenesis, super-resolution microscopy, APT2 eraser identification, high-fat-diet mouse models

    PMID:38016475 PMID:39141356 PMID:39255795

    Open questions at the time
    • How three distinct palmitoylation events coordinate temporally and spatially unclear
    • Whether palmitoylation affects phase separation not tested
  16. 2024 High

    MAVS was shown to directly bind cellular mRNA 3' UTRs through its intrinsically disordered central domain, and RNase-mediated RNA removal disrupted the MAVS signalosome and abolished IRF3 phosphorylation, revealing RNA as a structural component of the signaling complex.

    Evidence RNase treatment, RNA-protein pulldown, signalosome disruption assay, IRF3 phosphorylation assay

    PMID:39700280

    Open questions at the time
    • Identity of specific mRNAs required for signalosome integrity unknown
    • Whether RNA binding is regulated upon infection not determined
    • Structural role of RNA within MAVS aggregates/phase-separated condensates not visualized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: the atomic structure of full-length MAVS filaments, the spatiotemporal coordination of the numerous activating and inhibitory post-translational modifications, the relationship between prion-like aggregation and liquid-liquid phase separation, and the physiological significance of MAVS-dependent metabolic reprogramming in antiviral defense in vivo.
  • No cryo-EM or high-resolution structure of MAVS filaments
  • Integrated temporal model of PTM cross-talk during infection lacking
  • In vivo contribution of MAVS metabolic functions versus immune functions not separated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 6 GO:0003723 RNA binding 1
Localization
GO:0005739 mitochondrion 4 GO:0005777 peroxisome 2
Pathway
R-HSA-168256 Immune System 8 R-HSA-162582 Signal Transduction 5 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 2
Partners
DDX58IFIH1PRMT7PRMT9TBK1TRAF3TRAF6TRIM31
Complex memberships
MAVS signalosomeMAVS-NLRP3 inflammasome complexRIG-I-MAVS-TRAF signaling complex

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 MAVS was identified as a mitochondrial adaptor protein required for NF-κB and IRF3 activation downstream of RIG-I in response to viral infection. Its N-terminal CARD-like domain mediates interaction with RIG-I, and its C-terminal transmembrane domain targets it to the mitochondria; both domains are essential for signaling. RNA interference knockdown, overexpression, epistasis experiments, subcellular fractionation, domain mutagenesis Cell High 16125763
2005 IPS-1 (MAVS) activates IRF3, IRF7, and NF-κB via TBK1 and IKKi kinases; its N-terminal CARD-like domain mediates direct interaction with the CARDs of RIG-I and MDA5. Overexpression, siRNA knockdown, co-immunoprecipitation, functional reporter assays Nature immunology High 16127453
2005 VISA (MAVS) recruits IRF-3 to RIG-I and interacts with TRIF and TRAF6, mediating bifurcation of the TLR3-triggered NF-κB and IRF-3 activation pathways. Co-immunoprecipitation, siRNA knockdown, reporter assays Molecular cell High 16153868
2006 TRAF3 directly and specifically interacts with a TRAF-interaction motif (TIM) within MAVS/Cardif, and this interaction is required for MAVS-mediated type I IFN production; the TRAF domain of TRAF3 (but not TRAF5) binds the TIM of MAVS. Direct binding assays, mutagenesis of TRAF domain, co-immunoprecipitation, reporter assays, siRNA knockdown The EMBO journal High 16858409
2008 Crystal structure of the human MAVS CARD domain was determined at 2.1 Å resolution, revealing a six-helix bundle with Greek-key topology and asymmetric surface charge distribution typical of homotypic CARD-CARD interactions. X-ray crystallography of MBP-fusion protein BMC structural biology High 18307765
2008 MAVS (Cardif) is cleaved and inactivated by cellular caspases activated by pro-apoptotic signals, abolishing its capacity to activate IRF and NF-κB; poliovirus infection triggers caspase-dependent Cardif cleavage as an immune evasion strategy. In vitro cleavage assays, caspase inhibition, virus infection assays Cell death and differentiation Medium 18307765 30878284
2009 MAVS induces apoptosis independent of IFN-I production; MAVS-induced cell death requires mitochondrial localization, is caspase-dependent, and displays hallmarks of apoptosis. HCV NS3/4A and SARS-CoV NSP15 inhibit MAVS-mediated apoptosis. MAVS knockout fibroblasts, overexpression, caspase inhibitors, viral protein screens PloS one High 19404494
2009 PLK1 directly associates with MAVS via its Polo-box domain (PBD) through both phosphorylation-dependent (at STP motif, Thr234) and phosphorylation-independent (at C-terminus) interactions. PLK1 inhibits MAVS-mediated IRF3 and NF-κB activation by disrupting MAVS-TRAF3 association. Yeast two-hybrid, co-immunoprecipitation, mutagenesis, PLK1 depletion, phosphopeptide binding assays The Journal of biological chemistry High 19546225
2010 c-Abl tyrosine kinase physically associates with MAVS through its CARD and TM domains in vivo and in vitro, phosphorylates MAVS on tyrosine residues, and its functional impairment attenuates MAVS- or VSV-induced type I IFN production. Co-immunoprecipitation, in vitro binding, phosphotyrosine antibody detection, c-Abl kinase inhibition, siRNA knockdown FEBS letters Medium 19914245
2011 Viral infection induces MAVS to form large prion-like aggregates on the mitochondrial membrane that potently activate IRF3. Recombinant MAVS fibrils convert endogenous MAVS into functional aggregates in a prion-like manner. In the presence of K63-linked polyubiquitin chains, RIG-I catalyzes conversion of MAVS into prion-like aggregates. Biochemical fractionation, semi-denaturing detergent agarose gel electrophoresis (SDD-AGE), recombinant MAVS fibril reconstitution, in vitro IRF3 activation assay Cell High 21782231
2011 DHX9 helicase acts as a dsRNA sensor in myeloid dendritic cells by interacting with MAVS (IPS-1) via its HelicC-HA2-DUF domain binding to the CARD domain of MAVS, activating NF-κB and IRF3. siRNA knockdown, co-immunoprecipitation, dsRNA binding assay Journal of immunology Medium 21957149
2011 IFIT3 bridges TBK1 to MAVS on mitochondria by interacting with TBK1 N-terminus (K38) via its TPR motif (E164/E165), promoting TBK1 and IRF3 activation. Co-immunoprecipitation, mutagenesis, knockdown/overexpression, reporter assays Journal of immunology Medium 21813773
2011 PCBP1 mediates constitutive housekeeping degradation of MAVS, while PCBP2 acts as a post-infection feedback inhibitor; both suppress MAVS-mediated antiviral responses through promoting MAVS degradation. Co-immunoprecipitation, overexpression, siRNA knockdown, subcellular fractionation, western blot Cell research Medium 22105485
2013 MAVS associates with NLRP3 and facilitates its oligomerization leading to caspase-1 activation; mitochondrial localization of MAVS (requiring the transmembrane domain) is essential for NLRP3 inflammasome activation. Co-immunoprecipitation, reconstituted 293T cell system, MAVS-ΔTM mutant, MAVS knockdown in THP-1 and macrophages, Sendai virus infection Journal of immunology High 24048902
2014 MAVS activates a JNK2-specific apoptosis pathway via MAVS-MKK7-JNK2 signaling; MAVS recruits MKK7 to mitochondria via its 3D domain, which then phosphorylates JNK2 to trigger apoptosis. Genetic KO mice (Jnk1-/-, Jnk2-/-, Mkk7-/-), co-immunoprecipitation, domain mapping, viral challenge PLoS pathogens High 24651600
2014 Smurf2 E3 ubiquitin ligase targets MAVS for K48-linked ubiquitination and proteasomal degradation, negatively regulating virus-triggered type I IFN signaling; ligase-dead mutant (C716A) loses this activity. Co-immunoprecipitation, ubiquitination assays, E3 ligase mutagenesis, Smurf2 KO/knockdown Journal of immunology Medium 24729608
2014 Enterovirus 2Apro cleaves both MDA5 and MAVS during CVB3, poliovirus, and EV71 infection, blocking RLR pathway activation upstream of TBK1 phosphorylation and IRF3 phosphorylation, in a caspase- and proteasome-independent manner. Virus infection, protease inhibitor studies, western blot for cleavage products, TBK1/IRF3 phosphorylation assays Journal of virology High 24390337
2014 IPS-1 (MAVS) directly binds to PKR through its CARD domain, facilitates PKR autophosphorylation and dimerization, and promotes dsRNA-induced stress granule formation. Co-immunoprecipitation, pulldown assay, in vitro autophosphorylation assay, siRNA knockdown Journal of cell science Medium 24659800
2015 MAVS and STING harbor conserved serine and threonine clusters phosphorylated by IKK and/or TBK1 upon stimulation. Phosphorylated MAVS binds a positively charged surface of IRF3, recruiting IRF3 for TBK1-mediated phosphorylation and activation. In vitro kinase assays, mutagenesis of phosphorylation sites, pulldown of phospho-MAVS with IRF3, structural analysis of IRF3 surface Science High 25636800
2016 Autophagy negatively regulates MAVS activity through direct binding of LC3 to the LIR motif Y(9)xxI(12) of MAVS; c-Abl kinase phosphorylates MAVS tyrosine residues required for downstream signaling activation and modulates the MAVS-LC3 interaction. Co-immunoprecipitation, LIR motif mutagenesis, c-Abl kinase assay, MAVS KO mice, MPTP-induced model Cell death and differentiation Medium 28141795
2017 MAVS activates TBK1 and IKKε via TRAF proteins pre-associated with TBK1/IKKε through coiled-coil domain of TRAFs and SDD domain of TBK1/IKKε. TRAFs' E3 ligase activity synthesizes ubiquitin chains that bind NEMO to activate NF-κB and TBK1. TRAF2/3/5/6 quadruple-KO cells completely lost RNA virus responses. Multiple TRAF KO cell lines, co-immunoprecipitation, ubiquitination assays, domain interaction mapping PLoS pathogens High 29125880
2017 TRAF3IP3 accumulates on mitochondria upon virus infection and facilitates recruitment of TRAF3 to MAVS, enabling TBK1-IRF3 activation; MAVS-Region III multimerization state controls this downstream signaling. Co-immunoprecipitation, Traf3ip3-/- mice, viral challenge, TRAF3 recruitment assay The EMBO journal High 31390091
2017 Zyxin binds MAVS (identified by yeast two-hybrid), co-localizes on mitochondria, and acts as a scaffold stabilizing RIG-I/MDA5 interactions with MAVS; zyxin knockdown abrogates RLR-MAVS interactions and reduces IFN-β production. Yeast two-hybrid, co-immunoprecipitation, proximity ligation assay, siRNA knockdown Scientific reports Medium 28928438
2019 Apoptotic caspase-3 cleaves MAVS (at multiple alternative sites) to prevent cytokine overproduction; caspase-3 deficiency leads to elevated type I IFNs and increased resistance to viral infection. Caspase-3/7 KO cells, in vitro cleavage, Casp3-/- mice, viral infection assays Molecular cell High 30878284
2019 MAVS interacts with cPLA2 via CARD-C2 domain interaction in astrocytes, driving NF-κB-dependent CNS inflammation; this interaction also displaces hexokinase 2 (HK2) from MAVS, reducing HK enzymatic activity and lactate production. Proteomic, metabolomic, co-immunoprecipitation, perturbation studies in EAE model Cell High 31813625
2019 NLK kinase interacts with and phosphorylates MAVS at multiple sites on mitochondria and peroxisomes, inducing MAVS degradation and subsequent IRF3 inactivation; NLK depletion promotes antiviral cytokine production and viral resistance in mice. Co-immunoprecipitation, kinase assay with phosphorylation site mutagenesis, NLK KO/knockdown, in vivo VSV challenge Nature communications High 31324787
2019 MARCH5 mitochondrial E3 ubiquitin ligase degrades MAVS protein aggregates and also targets activated RIG-I oligomers for K48-linked ubiquitination at Lys193 and Lys203, switching off RLR signaling. In vivo ubiquitination assay, co-immunoprecipitation, proteasome inhibitor rescue, domain mapping Cellular signalling Medium 31881323
2020 RNF115 constitutively catalyzes K48-linked ubiquitination and proteasomal degradation of homeostatic MAVS in uninfected cells, keeping basal MAVS levels low; Rnf115-/- organs show substantially increased MAVS protein levels. Rnf115-/- mice, ubiquitination assays, protein stability assays, viral challenge Nature communications High 33139700
2020 MAVS interacts with p53 and recruits it to mitochondria under genotoxic stress; MAVS inhibits p53 ubiquitination by blocking the p53-MDM2 complex, stabilizing p53 and promoting p53-dependent cell death. Co-immunoprecipitation, MAVS KO mice, tumor models, MDM2 competition assay Cell reports Medium 31968249
2021 USP18 deubiquitinase specifically interacts with MAVS, promotes K63-linked polyubiquitination and aggregation of MAVS, and functions as a scaffold to facilitate TRIM31 re-localization and enhance TRIM31-MAVS interaction at mitochondria. Co-immunoprecipitation, ubiquitination assays, Usp18-/- mice, viral challenge Nature communications Medium 34016972
2021 PRMT7 catalyzes arginine monomethylation of MAVS at R52, attenuating MAVS binding to TRIM31 and RIG-I, suppressing MAVS aggregation and activation. Upon virus infection, SMURF1 is recruited to PRMT7 by MAVS to induce PRMT7 proteasomal degradation, relieving MAVS suppression. In vitro methylation assay, mutagenesis (R52A), co-immunoprecipitation, Prmt7-/- mice, viral challenge Molecular cell High 34171297
2021 SARS-CoV-2 Nsp5 promotes SUMOylation of MAVS to increase its protein stability and activate NF-κB signaling; SUMOylation inhibition or MAVS knockdown attenuates Nsp5-mediated NF-κB activation. Co-immunoprecipitation, SUMOylation assays, siRNA knockdown, reporter assays Frontiers in immunology Medium 34858407
2021 SARS-CoV-2 ORF10 induces mitophagy by interacting with mitophagy receptor NIX and LC3B, translocating to mitochondria and triggering MAVS degradation through the autophagy pathway, suppressing IFN-I signaling. Co-immunoprecipitation, NIX knockdown, autophagy/mitophagy assays, SARS-CoV-2 infection Cellular & molecular immunology Medium 34845370
2022 PRMT9 directly catalyzes arginine methylation of MAVS at Arg41 and Arg43, inhibiting MAVS aggregation and autoactivation in resting cells; upon virus infection, PRMT9 dissociates from mitochondria allowing MAVS aggregation. In vitro methylation assay, mutagenesis of methylation sites, PRMT9 knockdown/KO, MAVS aggregation assay Nature communications High 36028484
2023 PIAS3-induced poly-SUMOylation promotes K63-linked polyubiquitination and aggregation of MAVS, and SUMO conjugation enables MAVS phase separation via a SUMO-interacting motif (SIM) in MAVS. IRF3 contains a SIM that mediates enrichment to MAVS droplets; IRF3 phosphorylation disables SUMO-SIM interactions to release activated IRF3. SENP1 deSUMOylates MAVS, inhibiting its aggregation and IRF3 recruitment. SUMOylation assays, phase separation experiments, SIM mutagenesis, IRF3 recruitment assays, SENP1 KO Nature structural & molecular biology High 37188808
2023 EBV-encoded BILF1 associates with MAVS and the UFM1 E3 ligase UFL1, directing UFMylation of MAVS that triggers MAVS packaging into mitochondrial-derived vesicles and lysosomal proteolysis, suppressing NLRP3 inflammasome activation. AP-MS protein interaction mapping, co-immunoprecipitation, UFMylation assays, BILF1 KO viral replication Molecular cell High 37311461
2023 CPT1A recruits ZDHHC4 to catalyze MAVS palmitoylation at Cys79, which promotes MAVS stabilization by inhibiting K48- but facilitating K63-linked ubiquitination, leading to MAVS activation and IFN-I response. Palmitoylation assays, ZDHHC4 co-immunoprecipitation, ubiquitination assays, mutagenesis of Cys79 Molecular cell High 38016475
2023 The unanchored K63-linked polyubiquitin chains loaded on MAVS are directly recognized by RIG-I to initiate MAVS aggregation; Ube2N cooperates with E3 ligases Riplet and TRIM31 to promote unanchored K63-linked polyubiquitination of MAVS, while USP10 removes these chains and attenuates MAVS aggregation. Ubiquitination assays, Ube2N/USP10 KO, RIG-I CARD binding assays, MAVS aggregation (SDD-AGE) Cellular & molecular immunology High 37582970
2023 Peroxisomal MAVS interacts with G6PD and recruits TRAF6 and IRF1 to drive glucose flux into the pentose phosphate pathway and type III IFN expression; MAMs-located MAVS interacts with GFPT and recruits TRAF6 and TRAF2 to shift flux into the hexosamine biosynthesis pathway and type I IFN expression. Subcellular fractionation, co-immunoprecipitation, MAVS KO, glucose metabolic tracing Nature communications Medium 37660168
2023 TRIM28 targets MAVS for proteasome-mediated degradation via K48-linked polyubiquitination at K7, K10, K371, K420, and K500 residues; the RING domain (Cys65 and Cys68) is critical for this activity. Ubiquitination assays, site-specific mutagenesis, TRIM28 overexpression/knockdown, proteasome inhibitor rescue The Journal of biological chemistry Medium 37119745
2023 UBL7 promotes K27-linked polyubiquitination of MAVS by interacting with E3 ligase TRIM21 and facilitating TRIM21-MAVS complex formation, enhancing TBK1 recruitment to the MAVS complex. Co-immunoprecipitation, ubiquitination assays, Ubl7-/- mice, viral challenge Cell reports Medium 36943869
2024 MAVS is S-palmitoylated by ZDHHC7 at Cys508 (adjacent to the tail-anchor transmembrane helix); upon viral infection, this palmitoylation stabilizes MAVS aggregation on the mitochondrial outer membrane and promotes antiviral signaling propagation without affecting basal mitochondrial localization. Palmitoylation assay (acyl-RAC), ZDHHC7 co-immunoprecipitation, Cys508 mutagenesis, super-resolution microscopy, MAVS aggregation assay Proceedings of the National Academy of Sciences High 39141356
2024 ZDHHC24 catalyzes MAVS palmitoylation in response to palmitic acid, enhancing MAVS aggregation and activating the TBK1-IRF3-IFN pathway; APT2 de-palmitoylates MAVS to inhibit antiviral signaling. Palmitoylation assay, ZDHHC24 knockdown, APT2 inhibitor (ML349), high-fat-diet mouse models Molecular cell High 39255795
2024 MAVS directly interacts with the 3' UTRs of cellular mRNAs through its central intrinsically disordered domain; RNA elimination by RNase treatment disrupts the MAVS signalosome and inhibits phosphorylation of transcription factors that induce interferons. RNase treatment, RNA-protein pulldown, MAVS signalosome disruption assay, IRF3 phosphorylation assay Science High 39700280
2023 MAVS interacts with OPA1 GTPase; loss of MAVS or OPA1 leads to mitochondrial structural dysfunction and cellular senescence in human mesenchymal stem cells, independent of antiviral signaling. CRISPR/Cas9 MAVS KO hMSCs, co-immunoprecipitation with OPA1, mitochondrial morphology assays, senescence markers Research Medium 37521327
2019 Influenza A M2 protein colocalizes and interacts with MAVS on mitochondria; M2's proton channel activity induces ROS production, promoting autophagy that controls MAVS aggregation, thereby enhancing MAVS signaling. Co-immunoprecipitation, confocal microscopy, ROS measurement, autophagy assays, proton channel mutant M2 Autophagy Medium 30741586
2018 RIG-I-MAVS-TRAF6 signaling axis activates autophagy by recruiting Beclin-1 to mitochondria where TRAF6 catalyzes K63-linked polyubiquitination of Beclin-1, triggering the autophagic process as a negative feedback mechanism. MAVS KO, TRAF6 KO, co-immunoprecipitation, ubiquitination assays, Beclin-1 translocation assay Frontiers in immunology Medium 30258449
2008 MAVS is expressed as multiple protein isoforms from three splice variants (MAVS 1a, 1b, 1c); MAVS 1b selectively activates IRF3/IFN-β but not NF-κB, interacts with RIP1 and FADD, and exhibits antiviral activity against VSV. cDNA cloning, overexpression, reporter assays, co-immunoprecipitation Molecular immunology Medium 18207245
2017 RIG-I, TRIM25, and MAVS form distinct subcellular complexes; TRIM25 redistributes to stress granules upon activation, RIG-I associates with TRIM25/stress granules and mitochondrial MAVS, and MAVS competes with TRIM25 for RIG-I binding—suggesting activated RIG-I moves from TRIM25 to MAVS at mitochondria. Bimolecular fluorescence complementation (BiFC), super-resolution microscopy, live cell imaging in virus-infected cells Journal of virology Medium 27807226

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Identification and characterization of MAVS, a mitochondrial antiviral signaling protein that activates NF-kappaB and IRF 3. Cell 2748 16125763
2005 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nature immunology 2090 16127453
2015 Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science (New York, N.Y.) 1587 25636800
2005 VISA is an adapter protein required for virus-triggered IFN-beta signaling. Molecular cell 1562 16153868
2011 MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell 1065 21782231
2006 Essential role of IPS-1 in innate immune responses against RNA viruses. The Journal of experimental medicine 407 16785313
2006 Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif. The EMBO journal 349 16858409
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