Affinage

MAVS

Mitochondrial antiviral-signaling protein · UniProt Q7Z434

Length
540 aa
Mass
56.5 kDa
Annotated
2026-06-10
100 papers in source corpus 47 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 9/9 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAVS is a mitochondrial outer membrane adaptor protein that serves as the central hub for cytosolic RNA virus sensing, transducing signals from the RIG-I/MDA5 receptors into type I interferon and NF-κB responses (PMID:16125763, PMID:16785313). Its N-terminal CARD domain engages activated RIG-I and MDA5 through homotypic CARD–CARD interactions, while the C-terminal transmembrane domain anchors it to mitochondria; both are essential for signaling (PMID:16125763, PMID:16127453, PMID:18307765). Upon activation, RIG-I bound to K63-linked polyubiquitin chains nucleates MAVS into self-propagating prion-like aggregates on the mitochondrial membrane that potently activate IRF3, with membrane tethering restraining polymerization (PMID:21782231, PMID:37582970, PMID:30715798). Aggregated MAVS recruits TRAF2/3/5/6, which deliver pre-associated TBK1/IKKε and activate NEMO-dependent IKK to phosphorylate the kinases; assembly is bridged by accessory factors including TRAF3IP3 and IFIT3 (PMID:29125880, PMID:31390091, PMID:21813773, PMID:16858409). Phosphorylated MAVS then directly binds a positively charged surface of IRF3 to license its TBK1-mediated activation and IFN-β induction, a mechanism shared with STING and TRIF (PMID:25636800). Signalosome organization further depends on direct binding of cellular mRNA 3'UTRs through the MAVS intrinsically disordered region and on SUMO/SIM-driven phase separation (PMID:39700280, PMID:37188808). MAVS function is governed by an extensive code of post-translational modifications: K63/K27-linked ubiquitination and palmitoylation (ZDHHC4/7/24 at Cys79/Cys508) promote aggregation and activation, whereas K48-linked ubiquitination (RNF115, RNF90, RNF146/Tankyrase-PARylation), arginine methylation (PRMT7/PRMT9 at R41/R43/R52), and phosphodegradation by NLK or PLK1 restrain or terminate signaling (PMID:38016475, PMID:39141356, PMID:39255795, PMID:33139700, PMID:34512666, PMID:35733260, PMID:34171297, PMID:36028484, PMID:31324787, PMID:19546225). Beyond interferon induction, MAVS independently drives virus-induced apoptosis via an MKK7–JNK2 axis, NLRP3 inflammasome activation, autophagy through LC3 and TRAF6 binding, metabolic reprogramming at peroxisomes and MAMs, and p53 stabilization (PMID:24651600, PMID:24048902, PMID:27551434, PMID:37660168, PMID:31968249). Its activity is a frequent target of viral immune evasion, exemplified by HCV NS3-4A cleavage at Cys508 that displaces MAVS from mitochondria (PMID:16177806, PMID:16731946).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 2005 High

    Established the existence and core architecture of a mitochondrial adaptor linking cytosolic RNA receptors to antiviral transcription, answering how RIG-I/MDA5 signals reach IRF3 and NF-κB.

    Evidence RNAi, overexpression, epistasis, domain deletion and subcellular fractionation across four independent groups (MAVS/IPS-1/Cardif/VISA)

    PMID:16125763 PMID:16127453 PMID:16153868 PMID:16177806

    Open questions at the time
    • Mechanism of MAVS activation by upstream receptors not defined
    • Stoichiometry and higher-order organization unknown
  2. 2005 High

    Showed MAVS is a target of viral immune evasion, framing it as a physiologically critical node, by demonstrating HCV NS3-4A proteolytic inactivation.

    Evidence NS3-4A protease cleavage assay with reporter readouts

    PMID:16177806

    Open questions at the time
    • Cleavage site and consequence for localization not yet mapped
  3. 2006 High

    Defined MAVS as the non-redundant adaptor for both RIG-I and MDA5 in vivo and mapped its direct recruitment of TRAF3, establishing genetic necessity and a key effector link.

    Evidence IPS-1 knockout mice with RNA virus challenge; TRAF3-TIM interaction mapping by mutagenesis and in vitro binding; NS3-4A localization studies

    PMID:16731946 PMID:16785313 PMID:16858409

    Open questions at the time
    • How TRAF recruitment is converted to kinase activation not resolved
    • DNA virus independence implies pathway boundary not characterized here
  4. 2008 High

    Determined the MAVS CARD fold and provided structural rationale for homotypic CARD-CARD signaling interactions.

    Evidence X-ray crystallography of the human MAVS CARD at 2.1 Å

    PMID:18307765

    Open questions at the time
    • Structure does not show RIG-I-bound or polymeric state
    • No information on full-length or membrane-embedded protein
  5. 2008 Medium

    Identified caspase cleavage as a regulatory off-switch, addressing how apoptotic signals intersect with antiviral signaling.

    Evidence Caspase cleavage assays and poliovirus infection with reporter readouts

    PMID:18756281

    Open questions at the time
    • Cleavage sites and in vivo relevance not defined
    • Single-lab biochemistry
  6. 2011 High

    Revealed the central activation mechanism: MAVS forms prion-like aggregates that propagate and amplify signaling, answering how a transient receptor signal is converted to robust IRF3 activation.

    Evidence SDD-AGE, recombinant CARD fibril seeding, and cell-free reconstitution with K63-polyUb and RIG-I

    PMID:21782231

    Open questions at the time
    • Physiological aggregate size and structure debated
    • How aggregation is spatially limited not addressed here
  7. 2011 Medium

    Began assembling the kinase-recruitment scaffold, identifying IFIT3 as a bridge that recruits TBK1 to the MAVS complex.

    Evidence Reciprocal Co-IP, domain mutagenesis, knockdown reporter assays

    PMID:21813773

    Open questions at the time
    • Stoichiometry within the signalosome unknown
    • Single-lab data
  8. 2015 High

    Solved how MAVS hands the signal to IRF3, showing IKK/TBK1-phosphorylated MAVS directly recruits IRF3 via a charged surface for activation — a mechanism conserved across STING and TRIF.

    Evidence In vitro kinase assays, phosphopeptide-IRF3 binding, mutagenesis with structural rationale

    PMID:25636800

    Open questions at the time
    • Identity of all phosphosites in vivo incompletely defined
    • Coupling to aggregation state not fully resolved
  9. 2017 High

    Resolved the kinase-activation logic, showing TRAFs bridge pre-associated TBK1/IKKε to MAVS and TRAF ubiquitin chains activate NEMO/IKK to phosphorylate the kinases.

    Evidence TRAF quadruple-knockout and NEMO-knockout cells with epistasis and Co-IP

    PMID:29125880

    Open questions at the time
    • Precise chain architecture and NEMO sensing details not fully mapped
  10. 2019 High

    Expanded MAVS beyond interferon to direct effector functions, establishing a dedicated MKK7-JNK2 apoptotic axis and accessory bridging by TRAF3IP3.

    Evidence Jnk1/Jnk2/Mkk7 knockout cells and mice, domain mapping, Co-IP; Traf3ip3 knockout mice with viral challenge

    PMID:24651600 PMID:31390091

    Open questions at the time
    • How MAVS selects between IFN, apoptotic, and inflammasome outputs not defined
  11. 2019 High

    Defined negative regulation of MAVS by kinase-driven degradation and constitutive K48-ubiquitination, explaining how basal levels and signal termination are enforced.

    Evidence NLK kinase assay and knockout mice; RNF115 in vivo ubiquitination and Rnf115-/- cells; caspase-3/7 knockout cells and mice

    PMID:30878284 PMID:31324787 PMID:33139700

    Open questions at the time
    • Interplay between competing modifications on the same molecule unresolved
  12. 2022 High

    Established the methylation/PARylation brake that prevents spontaneous MAVS aggregation in resting cells and is relieved upon infection.

    Evidence In vitro methylation and PARylation assays, site mutagenesis (R41/R43/R52, E137), PRMT7/PRMT9/TNKS1/2 knockout mice and SDD-AGE

    PMID:34171297 PMID:35733260 PMID:36028484

    Open questions at the time
    • How modifications are coordinately reversed upon infection only partly mapped
  13. 2023 High

    Identified palmitoylation and SUMO-driven phase separation as activating layers that stabilize MAVS aggregation and IRF3 partitioning.

    Evidence Palmitoylation assays with site mutagenesis (Cys79/Cys508) and ZDHHC4/7 identification; SUMOylation, SIM mutagenesis and phase-separation assays

    PMID:37188808 PMID:38016475 PMID:39141356

    Open questions at the time
    • Temporal ordering of palmitoylation, SUMOylation and ubiquitination unclear
  14. 2023 Medium

    Broadened MAVS into a metabolic and homeostatic hub, linking organelle-specific signalosomes to PPP/HBP flux and IFN class, and to mitochondrial integrity via OPA1.

    Evidence Organelle-specific MAVS constructs with metabolic flux assays (G6PD/GFPT at peroxisomes/MAMs); CRISPR MAVS knockout and OPA1 rescue

    PMID:37521327 PMID:37660168

    Open questions at the time
    • Causal contribution of metabolic outputs to antiviral defense not quantified
    • Single-lab studies
  15. 2024 High

    Revealed that signalosome assembly itself requires RNA, with MAVS binding cellular mRNA 3'UTRs through its disordered region to organize IRF3/IRF7 phosphorylation.

    Evidence RNA-IP, RNase disruption, disordered-domain deletion, phosphorylation and proteomic analyses

    PMID:39700280

    Open questions at the time
    • RNA-binding specificity and how RNA integrates with aggregation not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MAVS integrates its many competing modifications, RNA-binding, aggregation state and subcellular location to select among interferon, apoptotic, inflammasome, autophagic and metabolic outputs remains unresolved.
  • No unified model linking modification code to output choice
  • Quantitative thresholds for aggregation versus degradation unknown
  • Spatial coordination across mitochondria, peroxisomes and MAMs not mechanistically integrated

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060090 molecular adaptor activity 5 GO:0005198 structural molecule activity 2 GO:0003723 RNA binding 1
Localization
GO:0005739 mitochondrion 4 GO:0005777 peroxisome 2 GO:0005783 endoplasmic reticulum 2
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1643685 Disease 3 R-HSA-5357801 Programmed Cell Death 2
Partners
IFIT3IRF3OPA1RIG-ITBK1TRAF3TRAF3IP3TRAF6
Complex memberships
MAVS prion-like aggregate/signalosomeNLRP3 inflammasome

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2005 MAVS is a mitochondrial outer membrane protein with an N-terminal CARD-like domain and a C-terminal transmembrane domain; both domains are essential for signaling. MAVS activates NF-κB and IRF3 downstream of RIG-I upon viral infection, and its silencing by RNAi abolishes these responses. The transmembrane domain targets MAVS to the mitochondria. RNAi knockdown, overexpression, epistasis experiments, subcellular fractionation/localization, domain deletion mutagenesis, reporter assays Cell High 16125763
2005 MAVS (IPS-1) contains an N-terminal CARD-like domain that mediates direct interaction with the CARD domains of RIG-I and MDA5. TBK1 and IKKi kinases are required downstream of IPS-1 for interferon induction. Knockdown of IPS-1 blocks virus-induced interferon induction. Functional screening, co-immunoprecipitation (CARD-CARD interaction), siRNA knockdown, kinase requirement assays Nature immunology High 16127453
2005 MAVS (Cardif) interacts with RIG-I via CARD-CARD interaction and recruits IKKα, IKKβ, and IKKε through its C-terminal region to activate NF-κB and IRF3. HCV NS3-4A serine protease cleaves and inactivates Cardif as an immune evasion strategy. Co-immunoprecipitation, siRNA knockdown, overexpression reporter assays, NS3-4A protease cleavage assay Nature High 16177806
2005 MAVS (VISA) interacts with RIG-I, recruits IRF-3, and acts as a central scaffold. VISA also interacts with TRIF and TRAF6, mediating bifurcation of TLR3-triggered NF-κB and IRF-3 activation pathways. Depletion of VISA inhibits both TLR3-independent and TLR3-dependent IFN-β signaling. Co-immunoprecipitation, siRNA knockdown, reporter assays Molecular cell High 16153868
2006 HCV NS3-4A protease cleavage of MAVS dissociates it from the mitochondrial outer membrane, disrupting antiviral signaling. IKKε (but not TBK1) co-localizes strongly with MAVS at the mitochondrial membrane, and this co-localization is disrupted by NS3-4A. Mutation of Cys508 to Ala maintains mitochondrial localization in the presence of NS3-4A. Subcellular fractionation, confocal microscopy, site-directed mutagenesis (C508A), biochemical analysis Journal of virology High 16731946
2006 TRAF3 directly interacts with MAVS (Cardif) via a TRAF-interaction motif (TIM) in MAVS and the TRAF domain of TRAF3. This direct interaction is required for MAVS-mediated type I interferon production; mutations in two critical amino acids in the TRAF domain of TRAF3 that prevent TIM binding abolish IFN production. Co-immunoprecipitation, site-directed mutagenesis, in vitro binding assays, reporter assays The EMBO journal High 16858409
2006 IPS-1 (MAVS) is the sole adapter for both RIG-I and MDA5 signaling in vivo; IPS-1-deficient mice showed severe defects in type I interferon and inflammatory cytokine production and increased susceptibility to RNA (but not DNA) virus infection. Gene knockout mouse model, viral infection challenge, cytokine/IFN measurement The Journal of experimental medicine High 16785313
2008 Crystal structure of the human MAVS CARD domain determined at 2.1 Å resolution. The CARD adopts a six-helix bundle with Greek-key topology and asymmetric surface charge distribution characteristic of homotypic CARD-CARD interactions, with two major polar surfaces on opposite sides of the molecule. X-ray crystallography (MBP-fusion protein, 2.1 Å resolution) BMC structural biology High 18307765
2008 MAVS (Cardif) is cleaved and inactivated by cellular apoptotic caspases activated by various pro-apoptotic signals, resulting in loss of IRF and NF-κB activation capacity. Poliovirus infection triggers caspase-dependent cleavage of Cardif. Caspase cleavage assay, western blotting, reporter assays, viral infection Cell death and differentiation Medium 18756281
2009 MAVS induces apoptosis independently of its IFN-I induction function. MAVS-induced apoptosis requires mitochondrial localization and is caspase-dependent. MAVS-/- fibroblasts are resistant to Sendai virus-induced apoptosis. HCV NS3/4A and SARS-CoV NSP15 inhibit MAVS-induced apoptosis. MAVS knockout fibroblasts, overexpression, caspase inhibitor assay, domain localization, viral protein inhibition screen PloS one Medium 19404494
2009 PLK1 polo-box domain (PBD) associates with MAVS via two interactions: a phosphodependent interaction at Thr234 within an STP motif in the proline-rich domain, and a phosphoindependent interaction at the C-terminus. PLK1 inhibits MAVS-mediated IRF3/NF-κB activation and IFN induction by disrupting MAVS-TRAF3 association. Depletion of PLK1 increases IFN induction. Yeast two-hybrid, co-immunoprecipitation, site-directed mutagenesis, siRNA knockdown, reporter assays The Journal of biological chemistry Medium 19546225
2011 Viral infection induces MAVS to form very large prion-like aggregates on the mitochondrial membrane that potently activate IRF3. Recombinant MAVS CARD-domain fibrils can convert endogenous MAVS into functional aggregates (prion-like behavior). In the presence of K63-linked polyubiquitin chains, RIG-I catalyzes the conversion of MAVS on the mitochondrial membrane to prion-like aggregates. Semi-denaturing detergent agarose gel electrophoresis (SDD-AGE), recombinant protein fibril formation, in vitro IRF3 activation assay, cell-free system with purified components Cell High 21782231
2011 DHX9 helicase interacts with MAVS (IPS-1) via the HelicC-HA2-DUF domain of DHX9 and the CARD domain of IPS-1 to sense dsRNA in myeloid dendritic cells and activate NF-κB and IRF3. Co-immunoprecipitation, domain mapping, siRNA knockdown, reporter assays Journal of immunology Medium 21957149
2011 IFIT3 bridges MAVS and TBK1 by interacting with TBK1 via its TPR motif (E164/E165) and with the N-terminus of TBK1 (K38), thereby recruiting TBK1 to the MAVS complex on mitochondria and enabling IRF3 phosphorylation. Co-immunoprecipitation, site-directed mutagenesis, overexpression/knockdown, reporter assays Journal of immunology Medium 21813773
2011 PCBP1 mediates constitutive (housekeeping) degradation of MAVS to maintain basal MAVS levels, distinct from the post-infection inhibitor PCBP2. Overexpression of PCBP1 impairs MAVS-mediated antiviral responses; knockdown has the opposite effect. Overexpression, siRNA knockdown, subcellular fractionation, western blotting, reporter assays Cell research Medium 22105485
2013 MAVS directly associates with NLRP3 and facilitates its oligomerization, leading to caspase-1 activation. Mitochondrial localization of MAVS (transmembrane domain) is essential for this function; MAVS-ΔTM does not interact with NLRP3 or trigger its oligomerization. Co-immunoprecipitation, domain deletion mutagenesis (MAVS-ΔTM), reconstitution in 293T cells, siRNA knockdown in macrophages Journal of immunology Medium 24048902
2014 MAVS specifically activates JNK2 (but not JNK1 or other MAP kinases) through MKK7 to induce apoptosis during viral infection. MAVS recruits MKK7 onto mitochondria via its 3D domain, which phosphorylates JNK2. Jnk2-/- and Mkk7-/- cells cannot initiate virus-induced apoptosis. Gene knockout cells/mice (Jnk1-/-, Jnk2-/-, Mkk7-/-), domain deletion mutagenesis (3D domain), co-immunoprecipitation, viral challenge PLoS pathogens High 24651600
2015 MAVS harbors two conserved serine/threonine clusters that are phosphorylated by IKK and/or TBK1 in response to viral stimulation. Phosphorylated MAVS binds to a positively charged surface of IRF3, recruiting IRF3 for phosphorylation and activation by TBK1. This phosphorylation-dependent recruitment mechanism is conserved across MAVS, STING, and TRIF. In vitro kinase assay, site-directed mutagenesis, phosphopeptide binding assay, co-immunoprecipitation, structural analysis of IRF3 surface Science High 25636800
2016 MAVS directly interacts with LC3 through an LC3-binding motif 'YxxI', suggesting MAVS acts as an autophagy receptor for mitochondrial turnover. MAVS self-aggregation and interaction with TRAF2/6 are important for MAVS-mediated mitochondrial autophagy. MAVS activation is sufficient to induce autophagic signaling. Co-immunoprecipitation, LC3 binding motif mutagenesis, overexpression, autophagy assays Cell discovery Medium 27551434
2017 MAVS activates TBK1/IKKε through TRAFs; TRAFs pre-associated with TBK1/IKKε are recruited to MAVS via direct interaction between TRAF coiled-coil domains and the SDD domain of TBK1/IKKε. TRAF E3 ligase activity synthesizes ubiquitin chains that activate NEMO, which in turn activates IKKα/β to phosphorylate TBK1/IKKε. Cells lacking TRAF2, 3, 5, and 6 completely lose RNA virus responses. TRAF quadruple knockout cells, NEMO knockout cells, co-immunoprecipitation, reporter assays, epistasis analysis PLoS pathogens High 29125880
2017 Subcellular imaging shows that upon RIG-I activation, TRIM25 redistributes to cytoplasmic dots/stress granules while RIG-I associates with both TRIM25/stress granules and mitochondrial MAVS. MAVS competes with TRIM25 for RIG-I binding, suggesting RIG-I moves from TRIM25 to MAVS at mitochondria upon activation. HCV NS3/4A redistributes RIG-I/MAVS and MAVS/MAVS complexes but not RIG-I/TRIM25. Bimolecular fluorescence complementation (BiFC), super-resolution microscopy, co-immunoprecipitation, viral protein expression Journal of virology Medium 27807226
2019 Apoptotic caspase-3 (human cells) and caspase-7 (mouse cells) cleave MAVS (at multiple alternative sites) to prevent cytokine overproduction during viral infection. Caspase-3-deficient cells show elevated type I IFNs without infection, and Casp3-/- mice show increased resistance to viral infection. Caspase-3/7 knockout cells and mice, in vitro caspase cleavage assay, cytokine measurement, viral challenge Molecular cell High 30878284
2019 TRAF3IP3 accumulates on mitochondria upon virus infection and bridges TRAF3 to MAVS (specifically via MAVS Region III multimerization) to activate TBK1-IRF3. Traf3ip3-deficient mice have severely compromised interferon production and are vulnerable to RNA virus infection. Co-immunoprecipitation, Traf3ip3 knockout mice, domain analysis (MAVS Region III), viral challenge The EMBO journal High 31390091
2019 NLK kinase interacts with and phosphorylates MAVS at multiple sites on mitochondria and peroxisomes, inducing MAVS degradation and inactivation of IRF3. NLK depletion promotes antiviral cytokine production; NLK-deficient mice show increased survival after viral infection. Co-immunoprecipitation, in vitro kinase assay, NLK siRNA/knockout, site-directed mutagenesis, mouse viral challenge Nature communications High 31324787
2019 Sphingolipid metabolism in astrocytes triggers interaction of the C2 domain of cPLA2 with the CARD domain of MAVS, boosting NF-κB-driven pro-inflammatory transcription in CNS. cPLA2-MAVS interaction also disrupts MAVS-hexokinase 2 (HK2) interaction, decreasing HK2 enzymatic activity and lactate production that supports neurons. Proteomic, metabolomic, transcriptomic and perturbation studies, co-immunoprecipitation, domain interaction mapping, EAE mouse model Cell High 31813625
2019 RNF115 constitutively interacts with MAVS and induces K48-linked polyubiquitination and proteasomal degradation of MAVS in uninfected cells, keeping basal MAVS levels low. MAVS protein levels are substantially increased in Rnf115-/- cells/organs. After HSV-1 infection, RNF115 switches to catalyzing K63-linked ubiquitination of MITA instead. Co-immunoprecipitation, in vivo ubiquitination assay, Rnf115-/- mouse cells, western blotting, viral challenge Nature communications High 33139700
2020 RACK1 interacts with VISA/MAVS and attenuates RIG-I/VISA-mediated antiviral signaling by disrupting formation of VISA-TRAF2, VISA-TRAF3, and VISA-TRAF6 complexes. RACK1 enhances K48-linked ubiquitination of VISA and attenuates its K63-linked ubiquitination. Co-immunoprecipitation, siRNA knockdown, overexpression, in vivo ubiquitination assay, reporter assays Biochemical and biophysical research communications Medium 30527812
2021 USP18 interacts with MAVS at mitochondria and promotes K63-linked polyubiquitination and subsequent aggregation of MAVS by functioning as a scaffold that facilitates TRIM31 relocalization and enhances TRIM31-MAVS interaction. USP18-deficient mice are more susceptible to RNA virus infection. Co-immunoprecipitation, in vivo K63-ubiquitination assay, USP18 knockout mice, viral challenge, confocal microscopy Nature communications High 34016972
2021 PRMT7 forms aggregates and catalyzes MAVS arginine monomethylation at R52, attenuating MAVS binding to TRIM31 and RIG-I and suppressing MAVS aggregation. Upon virus infection, PRMT7 undergoes automethylation at R32, SMURF1 is recruited by MAVS to degrade PRMT7, relieving suppression. PRMT7-deficient mice show enhanced antiviral responses. In vitro methylation assay, co-immunoprecipitation, site-directed mutagenesis (R52, R32), PRMT7 knockout mice, viral challenge Molecular cell High 34171297
2021 RNF90 promotes K48-linked ubiquitination of MAVS leading to its proteasome-dependent degradation, negatively regulating RNA virus-triggered antiviral innate immune responses. RNF90-deficient cells and mice show enhanced antiviral responses. RNF90 knockout cells and mice, in vivo ubiquitination assay, co-immunoprecipitation, viral challenge Frontiers in immunology Medium 34512666
2022 PRMT9 directly targets MAVS and catalyzes arginine methylation at Arg41 and Arg43, inhibiting MAVS aggregation and autoactivation in resting cells. Upon virus infection, PRMT9 dissociates from mitochondria, allowing MAVS aggregation and activation. In vitro methylation assay, site-directed mutagenesis (R41, R43), co-immunoprecipitation, SDD-AGE aggregation assay Nature communications High 36028484
2022 Tankyrases 1/2 (TNKS1/2) translocate from cytosol to mitochondria upon viral infection, interact with MAVS, and catalyze PARylation of MAVS at Glu137, which primes MAVS for K48-linked polyubiquitination by RNF146 and subsequent proteasomal degradation. TNKS1/2-deficient mice produce higher IFN levels and have reduced viral loads. Co-immunoprecipitation, PARylation assay, site-directed mutagenesis (E137), in vivo ubiquitination assay, TNKS1/2 knockout mice, viral challenge Proceedings of the National Academy of Sciences High 35733260
2023 MAVS (at peroxisomes) interacts with G6PD and recruits TRAF6 and IRF1 to form the peroxisomal MAVS signalosome, driving glucose flux into the pentose phosphate pathway (PPP) and type III IFN expression. MAMs-located MAVS interacts with glutamine-fructose-6-phosphate transaminase and recruits TRAF6 and TRAF2 to drive glucose flux into HBP and type I IFN expression. Co-immunoprecipitation, subcellular fractionation, metabolic flux assays, organelle-specific MAVS constructs, reporter assays Nature communications Medium 37660168
2023 PIAS3-induced poly-SUMOylation of MAVS promotes K63-linked polyubiquitination and aggregation of MAVS. MAVS contains a SUMO-interacting motif (SIM) that enables phase separation and association with IRF3. SENP1 deSUMOylates MAVS to negatively regulate antiviral immunity. IRF3 contains a SIM that mediates its enrichment to MAVS droplets; IRF3 phosphorylation near SIM releases activated IRF3 from MAVS. Co-immunoprecipitation, site-directed mutagenesis (SIM, SUMOylation sites), phase separation assay, in vitro SUMOylation, SENP1 knockout/overexpression Nature structural & molecular biology High 37188808
2023 CPT1A recruits ZDHHC4 to catalyze MAVS Cys79-palmitoylation at the ER, promoting MAVS stabilization and activation by inhibiting K48-linked and facilitating K63-linked ubiquitination. Elevated CPT1A increases MAVS palmitoylation and amplifies the IFN-I response. Co-immunoprecipitation, palmitoylation assay, site-directed mutagenesis (C79), ubiquitination assay, CPT1A modulation, viral and tumor models Molecular cell High 38016475
2023 MAVS is S-palmitoylated by ZDHHC7 at Cys508, a residue adjacent to the transmembrane tail-anchor. Mitochondrial localization of MAVS at resting state depends on the transmembrane domain without Cys508 regulation; however, upon viral infection, Cys508 palmitoylation stabilizes MAVS aggregation on the mitochondrial outer membrane and promotes antiviral signaling. Site-directed mutagenesis (C508), palmitoylation assay, super-resolution microscopy, biochemical aggregation assays, viral challenge Proceedings of the National Academy of Sciences High 39141356
2023 K63-linked polyubiquitin chains loaded onto MAVS (including via unanchored linkage) are recognized by RIG-I CARD to initiate MAVS aggregation, requiring CARD-CARD (RIG-I:MAVS) interaction. Ube2N cooperates with E3 ligases Riplet and TRIM31 to promote unanchored K63-linked polyubiquitination of MAVS; USP10 removes these chains to attenuate RIG-I-mediated MAVS aggregation. USP10-deficient mice show enhanced resistance to RNA virus infection. In vitro ubiquitination reconstitution, Co-immunoprecipitation, SDD-AGE aggregation assay, USP10 knockout mice, viral challenge Cellular & molecular immunology High 37582970
2023 UBL7 promotes K27-linked polyubiquitination of MAVS by interacting with E3 ligase TRIM21 and enhancing TRIM21-MAVS interaction in a dose-dependent manner, facilitating TBK1 recruitment and IFN signaling. UBL7-deficient mice show increased susceptibility to viral infection. Co-immunoprecipitation, in vivo ubiquitination assay (K27-specific), UBL7 knockout mice, viral challenge Cell reports Medium 36943869
2023 EBV BILF1 associates with MAVS and the UFM1 E3 ligase UFL1, directing MAVS UFMylation. This triggers MAVS packaging into mitochondrial-derived vesicles and lysosomal proteolysis, preventing NLRP3 inflammasome activation during EBV replication. Protein interaction map (AP-MS), co-immunoprecipitation, UFMylation assay, lysosomal degradation assay, BILF1 knockout virus Molecular cell Medium 37311461
2023 MAVS directly interacts with MAVS through its interaction with OPA1 (GTPase); MAVS-OPA1 interaction maintains mitochondrial structural integrity in human mesenchymal stem cells. Loss of MAVS or OPA1 leads to mitochondrial dysfunction and accelerated cellular senescence. CRISPR/Cas9 MAVS knockout, co-immunoprecipitation, mitochondrial structure analysis, MAVS/OPA1 rescue experiments Research Medium 37521327
2024 MAVS directly interacts with cellular mRNA 3' UTRs through its central intrinsically disordered domain. RNA-dependent organization of the MAVS signalosome is required for IRF3/IRF7 phosphorylation and IFN induction; ribonuclease treatment disrupts the MAVS signalosome and inhibits downstream phosphorylation. RNA immunoprecipitation, ribonuclease (RNase) treatment, domain deletion mutagenesis (disordered domain), phosphorylation assays, proteomics of signalosome Science High 39700280
2024 ZDHHC24 catalyzes MAVS palmitoylation to promote TBK1-IRF3-IFN signaling; APT2 de-palmitoylates MAVS, inhibiting antiviral signaling. Palmitic acid induces MAVS palmitoylation and aggregation; APT2 inhibitor ML349 reverses MAVS inactivation and enhances antiviral responses. Palmitoylation assay, ZDHHC24/APT2 overexpression/knockdown, pharmacological inhibition (ML349), MAVS aggregation assay, viral challenge Molecular cell High 39255795
2020 MAVS stabilizes p53 by interacting with it, mediating p53 mitochondrial recruitment under genotoxic stress, and blocking the p53-MDM2 complex formation to inhibit p53 ubiquitination. MAVS knockout mice show decreased resistance to colon cancer in AOM/DSS models. Co-immunoprecipitation, MAVS knockout mice, tumor challenge (AOM/DSS), ubiquitination assay, p53 localization by fractionation Cell reports Medium 31968249
2021 SARS-CoV-2 Nsp5 promotes SUMOylation of MAVS, increasing MAVS protein stability and leading to NF-κB activation and pro-inflammatory cytokine induction. Knockdown of MAVS or inhibition of SUMOylation attenuates Nsp5-mediated NF-κB activation. Co-immunoprecipitation, SUMOylation assay, MAVS knockdown, SUMOylation inhibitor treatment, cytokine measurement Frontiers in immunology Medium 34858407
2019 MARCH5 E3 ubiquitin ligase targets MAVS protein aggregates for K48-linked ubiquitination and degradation (previously established); additionally targets activated RIG-I oligomers via the RING domain binding to the RIG-I CARD domain, transferring K48-linked polyubiquitin to Lys193 and Lys203 of RIG-I. Co-immunoprecipitation, in vivo ubiquitination assay, domain mapping (RING domain), site-directed mutagenesis (K193, K203 of RIG-I), proteasome inhibitor assay Cellular signalling Medium 31881323
2019 MAVS CARD domain forms fibrils of smaller than 80 nm in cells (not large prion fibrils as previously modeled). The transmembrane domain of MAVS is required for mitochondrial membrane remodeling, interferon signaling, and pro-apoptotic activities; membrane tethering restrains MAVS polymerization. Super-resolution light microscopy (STORM/PALM, 32 nm resolution), quantitative image analysis, domain deletion mutagenesis (TM domain), interferon/apoptosis reporter assays The FEBS journal Medium 30715798
2008 MAVS is expressed from a single gene with 6 exons but generates splice variants (1a, 1b, 1c) with distinct functions. Variant 1b selectively activates IFN-β but not IL-8 promoter and interacts with RIP1 and FADD. The N-terminal CARD domain interacts with RIG-I; putative TRAF2 and TRAF6 binding motifs modulate NF-κB activation. RT-PCR cloning, overexpression, reporter assays, co-immunoprecipitation Molecular immunology Medium 18207245

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 2767 16125763
2005 IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction. Nature immunology 2103 16127453
2005 Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus. Nature 1956 16177806
2015 Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation. Science (New York, N.Y.) 1623 25636800
2005 VISA is an adapter protein required for virus-triggered IFN-beta signaling. Molecular cell 1567 16153868
2011 MAVS forms functional prion-like aggregates to activate and propagate antiviral innate immune response. Cell 1075 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
2019 Apoptotic Caspases Suppress Type I Interferon Production via the Cleavage of cGAS, MAVS, and IRF3. Molecular cell 274 30878284
2013 The mitochondrial antiviral protein MAVS associates with NLRP3 and regulates its inflammasome activity. Journal of immunology (Baltimore, Md. : 1950) 223 24048902
2011 Orchestrating the interferon antiviral response through the mitochondrial antiviral signaling (MAVS) adapter. Current opinion in immunology 209 21865020
2015 How RIG-I like receptors activate MAVS. Current opinion in virology 194 25942693
2006 Dissociation of a MAVS/IPS-1/VISA/Cardif-IKKepsilon molecular complex from the mitochondrial outer membrane by hepatitis C virus NS3-4A proteolytic cleavage. Journal of virology 188 16731946
2010 IPS-1 is essential for the control of West Nile virus infection and immunity. PLoS pathogens 185 20140199
2017 MAVS activates TBK1 and IKKε through TRAFs in NEMO dependent and independent manner. PLoS pathogens 181 29125880
2019 Metabolic Control of Astrocyte Pathogenic Activity via cPLA2-MAVS. Cell 171 31813625
2009 MAVS-mediated apoptosis and its inhibition by viral proteins. PloS one 166 19404494
2020 Regulation of MAVS Expression and Signaling Function in the Antiviral Innate Immune Response. Frontiers in immunology 164 32536927
2011 Chicken cells sense influenza A virus infection through MDA5 and CARDIF signaling involving LGP2. Journal of virology 164 22072756
2013 Mechanisms of MAVS regulation at the mitochondrial membrane. Journal of molecular biology 162 24120683
2011 DHX9 pairs with IPS-1 to sense double-stranded RNA in myeloid dendritic cells. Journal of immunology (Baltimore, Md. : 1950) 157 21957149
2015 MAVS Coordination of Antiviral Innate Immunity. Journal of virology 152 25948741
2011 IFN-induced TPR protein IFIT3 potentiates antiviral signaling by bridging MAVS and TBK1. Journal of immunology (Baltimore, Md. : 1950) 146 21813773
2017 RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury. Science translational medicine 127 28424327
2019 Influenza M2 protein regulates MAVS-mediated signaling pathway through interacting with MAVS and increasing ROS production. Autophagy 110 30741586
2013 The evolution of vancomycin intermediate Staphylococcus aureus (VISA) and heterogenous-VISA. Infection, genetics and evolution : journal of molecular epidemiology and evolutionary genetics in infectious diseases 109 23567819
2021 USP18 positively regulates innate antiviral immunity by promoting K63-linked polyubiquitination of MAVS. Nature communications 105 34016972
2017 Regulation of MAVS activation through post-translational modifications. Current opinion in immunology 97 29245018
2014 RETRACTED: MAVS, cGAS, and endogenous retroviruses in T-independent B cell responses. Science (New York, N.Y.) 94 25525240
2011 Mutation of RNA polymerase beta subunit (rpoB) promotes hVISA-to-VISA phenotypic conversion of strain Mu3. Antimicrobial agents and chemotherapy 87 21746940
2008 Crystal structure of human IPS-1/MAVS/VISA/Cardif caspase activation recruitment domain. BMC structural biology 83 18307765
2009 Polo-like kinase 1 (PLK1) regulates interferon (IFN) induction by MAVS. The Journal of biological chemistry 80 19546225
2020 Autoimmunity gene IRGM suppresses cGAS-STING and RIG-I-MAVS signaling to control interferon response. EMBO reports 79 32715615
2017 Subcellular Localizations of RIG-I, TRIM25, and MAVS Complexes. Journal of virology 79 27807226
2020 RNF115 plays dual roles in innate antiviral responses by catalyzing distinct ubiquitination of MAVS and MITA. Nature communications 78 33139700
2018 Activation of RIG-I-Mediated Antiviral Signaling Triggers Autophagy Through the MAVS-TRAF6-Beclin-1 Signaling Axis. Frontiers in immunology 73 30258449
2021 SARS-CoV-2 Nsp5 Activates NF-κB Pathway by Upregulating SUMOylation of MAVS. Frontiers in immunology 72 34858407
2023 CircPVT1 promotes ER-positive breast tumorigenesis and drug resistance by targeting ESR1 and MAVS. The EMBO journal 71 37009655
2008 The antiviral adaptor proteins Cardif and Trif are processed and inactivated by caspases. Cell death and differentiation 69 18756281
2011 Poly(C)-binding protein 1 (PCBP1) mediates housekeeping degradation of mitochondrial antiviral signaling (MAVS). Cell research 68 22105485
2009 Cardif-mediated signaling controls the initial innate response to dengue virus in vivo. Journal of virology 66 19494017
2016 MAVS maintains mitochondrial homeostasis via autophagy. Cell discovery 64 27551434
2023 Pnpt1 mediates NLRP3 inflammasome activation by MAVS and metabolic reprogramming in macrophages. Cellular & molecular immunology 61 36596874
2023 An Epstein-Barr virus protein interaction map reveals NLRP3 inflammasome evasion via MAVS UFMylation. Molecular cell 58 37311461
2022 RNA binding by ADAR3 inhibits adenosine-to-inosine editing and promotes expression of immune response protein MAVS. The Journal of biological chemistry 58 35850307
2021 Arginine monomethylation by PRMT7 controls MAVS-mediated antiviral innate immunity. Molecular cell 57 34171297
2023 MAVS integrates glucose metabolism and RIG-I-like receptor signaling. Nature communications 56 37660168
2015 Identification and characterization of MAVS from black carp Mylopharyngodon piceus. Fish & shellfish immunology 55 25655327
2023 CPT1A induction following epigenetic perturbation promotes MAVS palmitoylation and activation to potentiate antitumor immunity. Molecular cell 53 38016475
2019 Phosphorylation of MAVS/VISA by Nemo-like kinase (NLK) for degradation regulates the antiviral innate immune response. Nature communications 51 31324787
2008 Identification of MAVS splicing variants that interfere with RIGI/MAVS pathway signaling. Molecular immunology 51 18207245
2021 MAVS: A Two-Sided CARD Mediating Antiviral Innate Immune Signaling and Regulating Immune Homeostasis. Frontiers in microbiology 46 34566944
2019 TRAF3IP3 mediates the recruitment of TRAF3 to MAVS for antiviral innate immunity. The EMBO journal 46 31390091
2014 MAVS-MKK7-JNK2 defines a novel apoptotic signaling pathway during viral infection. PLoS pathogens 43 24651600
2023 Senecavirus A-induced glycolysis facilitates virus replication by promoting lactate production that attenuates the interaction between MAVS and RIG-I. PLoS pathogens 42 37126525
2021 The MAVS Immune Recognition Pathway in Viral Infection and Sepsis. Antioxidants & redox signaling 42 34348482
2023 MAVS deSUMOylation by SENP1 inhibits its aggregation and antagonizes IRF3 activation. Nature structural & molecular biology 41 37188808
2022 The protein arginine methyltransferase PRMT9 attenuates MAVS activation through arginine methylation. Nature communications 39 36028484
2019 Dual targeting of RIG-I and MAVS by MARCH5 mitochondria ubiquitin ligase in innate immunity. Cellular signalling 36 31881323
2023 MAVS-loaded unanchored Lys63-linked polyubiquitin chains activate the RIG-I-MAVS signaling cascade. Cellular & molecular immunology 35 37582970
2022 Tankyrases inhibit innate antiviral response by PARylating VISA/MAVS and priming it for RNF146-mediated ubiquitination and degradation. Proceedings of the National Academy of Sciences of the United States of America 35 35733260
2021 Human Cancer Cells Sense Cytosolic Nucleic Acids Through the RIG-I-MAVS Pathway and cGAS-STING Pathway. Frontiers in cell and developmental biology 35 33490069
2014 MAVS protein is attenuated by rotavirus nonstructural protein 1. PloS one 33 24643253
2008 Molecular cloning and functional characterization of porcine IFN-beta promoter stimulator 1 (IPS-1). Veterinary immunology and immunopathology 33 18586328
2024 Cellular RNA interacts with MAVS to promote antiviral signaling. Science (New York, N.Y.) 32 39700280
2023 MAVS Antagonizes Human Stem Cell Senescence as a Mitochondrial Stabilizer. Research (Washington, D.C.) 32 37521327
2024 Targeting APT2 improves MAVS palmitoylation and antiviral innate immunity. Molecular cell 30 39255795
2024 MAVS Cys508 palmitoylation promotes its aggregation on the mitochondrial outer membrane and antiviral innate immunity. Proceedings of the National Academy of Sciences of the United States of America 28 39141356
2020 The Mitochondrial Protein MAVS Stabilizes p53 to Suppress Tumorigenesis. Cell reports 28 31968249
2008 Cleavage of the IPS-1/Cardif/MAVS/VISA does not inhibit T cell-mediated elimination of hepatitis C virus non-structural 3/4A-expressing hepatocytes. Gut 28 18689426
2019 Swine acute diarrhea syndrome coronavirus (SADS-CoV) antagonizes interferon-β production via blocking IPS-1 and RIG-I. Virus research 27 31884203
2017 Zyxin stabilizes RIG-I and MAVS interactions and promotes type I interferon response. Scientific reports 26 28928438
2014 IRF-3, IRF-7, and IPS-1 promote host defense against acute human metapneumovirus infection in neonatal mice. The American journal of pathology 26 24726644
2022 MAVS mediates a protective immune response in the brain to Rift Valley fever virus. PLoS pathogens 25 35584192
2019 Hepatovirus 3ABC proteases and evolution of mitochondrial antiviral signaling protein (MAVS). Journal of hepatology 25 30876947
2024 Nlrp6 protects from corticosterone-induced NSPC ferroptosis by modulating RIG-1/MAVS-mediated mitophagy. Redox biology 24 38772149
2021 Molecular Mechanisms of the Toll-Like Receptor, STING, MAVS, Inflammasome, and Interferon Pathways. mSystems 24 34184910
2021 Negative Regulation of RNF90 on RNA Virus-Triggered Antiviral Immune Responses Targeting MAVS. Frontiers in immunology 24 34512666
2023 Noncanonical MAVS signaling restrains dendritic cell-driven antitumor immunity by inhibiting IL-12. Science immunology 23 38039379
2023 MAVS signaling is required for preventing persistent chikungunya heart infection and chronic vascular tissue inflammation. Nature communications 21 37537212
2019 MAVS polymers smaller than 80 nm induce mitochondrial membrane remodeling and interferon signaling. The FEBS journal 21 30715798
2023 Flavivirus prM interacts with MDA5 and MAVS to inhibit RLR antiviral signaling. Cell & bioscience 20 36639652
2022 Viral protease cleavage of MAVS in genetically modified mice with hepatitis A virus infection. Journal of hepatology 20 36152761
2024 Gasdermin B, an asthma-susceptibility gene, promotes MAVS-TBK1 signalling and airway inflammation. The European respiratory journal 19 38514093
2020 PGAM5-MAVS interaction regulates TBK1/ IRF3 dependent antiviral responses. Scientific reports 19 32433485
2018 HAUS8 regulates RLR‑VISA antiviral signaling positively by targeting VISA. Molecular medicine reports 19 29916539
2018 RACK1 attenuates RLR antiviral signaling by targeting VISA-TRAF complexes. Biochemical and biophysical research communications 19 30527812
2021 microRNA-125a targets MAVS and TRAF6 to modulate interferon signaling and promote HCV infection. Virus research 17 33577860
2018 Goose MAVS functions in RIG-I-mediated IFN-β signaling activation. Developmental and comparative immunology 17 30557581
2020 Influenza PB1-F2 Inhibits Avian MAVS Signaling. Viruses 16 32272772
2019 Structural Variability in the RLR-MAVS Pathway and Sensitive Detection of Viral RNAs. Medicinal chemistry (Shariqah (United Arab Emirates)) 16 30569868
2006 VISA--a pass to innate immunity. The international journal of biochemistry & cell biology 16 17029998
2023 UBL7 enhances antiviral innate immunity by promoting Lys27-linked polyubiquitination of MAVS. Cell reports 15 36943869
2021 Mitochondrial morphology and MAVS-IFN1 signaling pathway in muscles of anti-MDA5 dermatomyositis. Annals of clinical and translational neurology 15 33576578
2019 NAC1 Potentiates Cellular Antiviral Signaling by Bridging MAVS and TBK1. Journal of immunology (Baltimore, Md. : 1950) 15 31235549
2018 Virus Infection Triggers MAVS Polymers of Distinct Molecular Weight. Viruses 15 29385716
2016 Activation of the RLR/MAVS Signaling Pathway by the L Protein of Mopeia Virus. Journal of virology 15 27605671
2022 MAVS Expression in Alveolar Macrophages Is Essential for Host Resistance against Aspergillus fumigatus. Journal of immunology (Baltimore, Md. : 1950) 14 35750336
2018 MAVS induces a host cell defense to inhibit CSFV infection. Archives of virology 14 29556776
2013 MAVS-mediated host cell defense is inhibited by Borna disease virus. The international journal of biochemistry & cell biology 14 23702035

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