The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
MAVS Forms Functional Prion-like Aggregates to Activate and Propagate Antiviral Innate Immune Response
Open accessAbstract
SUMMARY In response to viral infection, RIG-I–like RNA helicases bind to viral RNA and activate the mitochondrial protein MAVS, which in turn activates the transcription factors IRF3 and NF-κB to induce type-I interferons. We have previously shown that RIG-I binds to unanchored lysine-63 (K63) polyubiquitin chains and that this binding is important for MAVS activation; however, the mechanism underlying MAVS activation is not understood. Here we show that viral infection induces the formation of very large MAVS aggregates, which potently activate IRF3 in the cytosol. We find that a fraction of recombinant MAVS protein forms fibrils capable of activating IRF3. Remarkably, the MAVS fibrils behave like prions and effectively convert endogenous MAVS into functional aggregates. We also show that, in the presence of K63 ubiquitin chains, RIG-I catalyzes the conversion of MAVS on the mitochondrial membrane to prion-like aggregates. These results suggest that a prion-like conformational switch of MAVS activates and propagates the antiviral signaling cascade.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., et al. (2006) · Nature · doi:10.1038/nature04734 · Cited by 3,888
IPS-1, an adaptor triggering RIG-I- and Mda5-mediated type I interferon induction
Kawai, T., Takahashi, K., Sato, S., Coban, C., Kumar, H., Kato, H., Ishii, K. J., Takeuchi, O., & Akira, S. (2005) · Nature Immunology · doi:10.1038/ni1243 · Cited by 2,562
Cardif is an adaptor protein in the RIG-I antiviral pathway and is targeted by hepatitis C virus
Meylan, E., Curran, J., Hofmann, K., Moradpour, D., Binder, M., Bartenschlager, R., & Tschopp, J. (2005) · Nature · doi:10.1038/nature04193 · Cited by 2,401
RIG-I-mediated antiviral responses to single-stranded RNA bearing 5’-phosphates
Pichlmair, A., Schulz, O., Tan, C. P., Näslund, T. I., Liljeström, P., Weber, F., & Reis e Sousa, C. (2006) · Science · doi:10.1126/science.1132998 · Cited by 2,210
Nucleic acid recognition by the innate immune system
Barbalat, R., Ewald, S. E., Mouchess, M. L., & Barton, G. M. (2011) · Annual Review of Immunology · doi:10.1146/annurev-immunol-031210-101340 · Cited by 577
RIGorous Detection: Exposing Virus Through RNA Sensing
Rehwinkel, J., & Reis e Sousa, C. (2010) · Science · doi:10.1126/science.1185068 · Cited by 163
The prion hypothesis: from biological anomaly to basic regulatory mechanism
Tuite, M. F., & Serio, T. R. (2010) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3007 · Cited by 146
Cited by
Komander, D., & Rape, M. (2012) · Annual Review of Biochemistry · doi:10.1146/annurev-biochem-060310-170328 · Cited by 3,679
Phosphorylation of innate immune adaptor proteins MAVS, STING, and TRIF induces IRF3 activation
Liu, S., Cai, X., Wu, J., Cong, Q., Chen, X., Li, T., Du, F., Ren, J., Wu, Y.-T., Grishin, N. V., et al. (2015) · Science · doi:10.1126/science.aaa2630 · Cited by 1,927
Self-citationNF-κB, the first quarter-century: remarkable progress and outstanding questions
Hayden, M. S., & Ghosh, S. (2012) · Genes & Development · doi:10.1101/gad.183434.111 · Cited by 1,693
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases
Jucker, M., & Walker, L. C. (2013) · Nature · doi:10.1038/nature12481 · Cited by 1,663
Roulois, D., Loo Yau, H., Singhania, R., Wang, Y., Danesh, A., Shen, S. Y., Han, H., Liang, G., Jones, P. A., Pugh, T. J., et al. (2015) · Cell · doi:10.1016/j.cell.2015.07.056 · Cited by 1,527
Signaling in innate immunity and inflammation
Newton, K., & Dixit, V. M. (2012) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a006049 · Cited by 1,513
Innate Immune Pattern Recognition: A Cell Biological Perspective
Brubaker, S. W., Bonham, K. S., Zanoni, I., & Kagan, J. C. (2015) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032414-112240 · Cited by 1,475
Li, J., McQuade, T., Siemer, A. B., Napetschnig, J., Moriwaki, K., Hsiao, Y.-S., Damko, E., Moquin, D., Walz, T., McDermott, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.06.019 · Cited by 1,222
Mitochondria in the Regulation of Innate and Adaptive Immunity
Weinberg, S. E., Sena, L. A., & Chandel, N. S. (2015) · Immunity · doi:10.1016/j.immuni.2015.02.002 · Cited by 960
Chen, X., He, W.-T., Hu, L., Li, J., Fang, Y., Wang, X., Xu, X., Wang, Z., Huang, K., & Han, J. (2016) · Cell Research · doi:10.1038/cr.2016.100 · Cited by 831
The adaptor ASC has extracellular and 'prionoid' activities that propagate inflammation
Franklin, B. S., Bossaller, L., De Nardo, D., Ratter, J. M., Stutz, A., Engels, G., Brenker, C., Nordhoff, M., Mirandola, S. R., Al-Amoudi, A., et al. (2014) · Nature Immunology · doi:10.1038/ni.2913 · Cited by 773
Mitochondria: master regulators of danger signalling
Galluzzi, L., Kepp, O., & Kroemer, G. (2012) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3479 · Cited by 733
Yun, J., & Finkel, T. (2014) · Cell Metabolism · doi:10.1016/j.cmet.2014.01.011 · Cited by 626
The IκB kinase complex in NF‐κB regulation and beyond
Hinz, M., & Scheidereit, C. (2014) · The EMBO Reports · doi:10.1002/embr.201337983 · Cited by 572
The role of mitochondria in NLRP3 inflammasome activation
Liu, Q., Zhang, D., Hu, D., Zhou, X., & Zhou, Y. (2018) · Molecular Immunology · doi:10.1016/j.molimm.2018.09.010 · Cited by 475
Biology and Genetics of Prions Causing Neurodegeneration
Prusiner, S. B. (2013) · Annual Review of Genetics · doi:10.1146/annurev-genet-110711-155524 · Cited by 455
Mitochondria and cell signalling
Tait, S. W. G., & Green, D. R. (2012) · Journal of Cell Science · doi:10.1242/jcs.099234 · Cited by 453
Breaching Self-Tolerance to Alu Duplex RNA Underlies MDA5-Mediated Inflammation
Ahmad, S., Mu, X., Yang, F., Greenwald, E., Park, J. W., Jacob, E., Zhang, C.-Z., & Hur, S. (2018) · Cell · doi:10.1016/j.cell.2017.12.016 · Cited by 449
Double-Stranded RNA Sensors and Modulators in Innate Immunity
Hur, S. (2019) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042718-041356 · Cited by 420
Mitochondria in innate immune signaling
Banoth, B., & Cassel, S. L. (2018) · Translational Research · doi:10.1016/j.trsl.2018.07.014 · Cited by 410
Mitochondria: diversity in the regulation of the NLRP3 inflammasome
Gurung, P., Lukens, J. R., & Kanneganti, T.-D. (2015) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2014.11.008 · Cited by 393
ASC filament formation serves as a signal amplification mechanism for inflammasomes
Dick, M. S., Sborgi, L., Rühl, S., Hiller, S., & Broz, P. (2016) · Nature Communications · doi:10.1038/ncomms11929 · Cited by 394
Neurodegenerative Diseases: Expanding the Prion Concept
Walker, L. C., & Jucker, M. (2015) · Annual Review of Neuroscience · doi:10.1146/annurev-neuro-071714-033828 · Cited by 361
Sirt3 promotes antimycobacterial defenses by coordinating mitochondrial and autophagic functions
Kim, T. S., Jin, Y. B., Kim, Y. S., Kim, S., Kim, J. K., Lee, H.-M., Suh, H.-W., Choe, J. H., Kim, Y. J., Koo, B.-S., et al. (2019) · Autophagy · doi:10.1080/15548627.2019.1582743 · Cited by 172
Zhao, Y., Sun, X., Nie, X., Sun, L., Tang, T.-S., Chen, D., & Sun, Q. (2012) · PLoS Pathogens · doi:10.1371/journal.ppat.1003086 · Cited by 129
Drisaldi, B., Colnaghi, L., Fioriti, L., Rao, N., Myers, C., Snyder, A. M., Metzger, D. J., Tarasoff, J., Konstantinov, E., Fraser, P. E., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.04.061 · Cited by 120
Chen, J., Harding, S. M., Natesan, R., Tian, L., Benci, J. L., Li, W., Minn, A. J., Asangani, I. A., & Greenberg, R. A. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108080 · Cited by 111
Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids
Hu, M.-M., & Shu, H.-B. (2018) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev-cellbio-100617-062903 · Cited by 110
Enteroviruses: A Gut-Wrenching Game of Entry, Detection, and Evasion
Wells, A. I., & Coyne, C. B. (2019) · Viruses · doi:10.3390/v11050460 · Cited by 109
TBK1, a central kinase in innate immune sensing of nucleic acids and beyond
Zhou, R., Zhang, Q., & Xu, P. (2020) · Acta Biochimica et Biophysica Sinica · doi:10.1093/abbs/gmaa051 · Cited by 104
Powering the Immune System: Mitochondria in Immune Function and Deficiency
Walker, M. A., Volpi, S., Sims, K. B., Walter, J. E., & Traggiai, E. (2014) · Journal of Immunology Research · doi:10.1155/2014/164309 · Cited by 83
“RLRs have been most strongly linked to viral immunity via interactions with the mitochondrial antiviral signaling protein (MAVS) that in turn activates NF-kappaB and IRF3 [17, 18].”
TANK-binding kinase 1 as a novel therapeutic target for viral diseases
Zhao, C., & Zhao, W. (2019) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2019.1601702 · Cited by 61
Faizan, M. I., Chaudhuri, R., Sagar, S., Albogami, S., Chaudhary, N., Azmi, I., Akhtar, A., Ali, S. M., Kumar, R., Iqbal, J., et al. (2022) · Cells · doi:10.3390/cells11192969 · Cited by 61
Li, S.-Z., Shu, Q.-P., Song, Y., Zhang, H.-H., Liu, Y., Jin, B.-X., Liuyu, T.-Z., Li, C., Huang, X.-C., Du, R.-L., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11258-x · Cited by 59
Di Giorgio, E., & Xodo, L. E. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.917998 · Cited by 39
Reprogramming of mitochondrial metabolism by innate immunity
Garaude, J. (2019) · Current Opinion in Immunology · doi:10.1016/j.coi.2018.09.010 · Cited by 33
Luo, Z., Liu, L.-F., Jiang, Y.-N., Tang, L.-P., Li, W., Ouyang, S.-H., Tu, L.-F., Wu, Y.-P., Gong, H.-B., Yan, C.-Y., et al. (2020) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-020-00238-z · Cited by 34
“Stress/CORT impeded MAVS antiviral signaling MAVS can potently activate IRF3 and propagate IFNs and ISGs, which plays a crucial role in defending RNA virus infection.(20,21) We thus investigated the effect of stress/CORT on MAVS antiviral signaling pathway.”
Jia, B., Shen, Z., Zhu, S., Huang, J., Liao, Z., Zhao, S., Li, H., Chen, S., Xu, Y., Wang, Y., et al. (2025) · Cell · doi:10.1016/j.cell.2025.07.047 · Cited by 25
A nucleation barrier spring-loads the CBM signalosome for binary activation
Rodriguez Gama, A., Miller, T., Lange, J. J., Unruh, J. R., & Halfmann, R. (2022) · eLife · doi:10.7554/elife.79826 · Cited by 18
Contrasting functions of ATP hydrolysis by MDA5 and LGP2 in viral RNA sensing
Singh, R., Wu, Y., Herrero del Valle, A., Leigh, K. E., Mong, S., Cheng, M. T. K., Ferguson, B. J., & Modis, Y. (2024) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2024.105711 · Cited by 16
Contrasting functions of ATP hydrolysis by MDA5 and LGP2 in viral RNA sensing
Singh, R., Wu, Y., Herrero del Valle, A., Leigh, K. E., Cheng, M. T. K., Ferguson, B. J., & Modis, Y. (2023) · doi:10.1101/2023.05.25.542247
Metadata
- Authors
- Hou, F., Sun, L., Zheng, H., Skaug, B., Jiang, Q.-X., & Chen, Z. J.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2011-08
- Volume
- 146
- Issue
- 3
- Pages
- 448-461
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2053476949
- Cited by
- 1,282
- References
- 7
- FWCI
- 30.80
- Type
- journal article
- Language
- en
- Open access
- bronze
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
