Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Abstract
The innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds)RNA) and triggers antiviral responses. The cytoplasmic helicase proteins RIG-I (retinoic-acid-inducible protein I, also known as Ddx58) and MDA5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) have been implicated in viral dsRNA recognition. In vitro studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine-polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue. Although a critical role for RIG-I in the recognition of several RNA viruses has been clarified, the functional role of MDA5 and the relationship between these dsRNA detectors in vivo are yet to be determined. Here we use mice deficient in MDA5 (MDA5-/-) to show that MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs. RNA viruses are also differentially recognized by RIG-I and MDA5. We find that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxoviruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection. Furthermore, RIG-I-/- and MDA5-/- mice are highly susceptible to infection with these respective RNA viruses compared to control mice. Together, our data show that RIG-I and MDA5 distinguish different RNA viruses and are critical for host antiviral responses.
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Several RNA structural features are immunostimulatory due to interactions with RNA sensors such as Toll-like receptors, RIG-I, and PKR.
“However, several RNA structural features have been described as immunostimulatory due to interactions with various RNA sensors such as Toll-like receptors, RIG-I, and PKR.”
From Sequence-engineered mRNA without chemical nucleoside modifications enables an effective protein therapy in large animals (2015) · cites this paper as [11]
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Pathogen Recognition and Innate Immunity
Akira, S., Uematsu, S., & Takeuchi, O. (2006) · Cell · doi:10.1016/j.cell.2006.02.015 · Cited by 11,974 · see citing works
Recognition of double-stranded RNA and activation of NF-κB by Toll-like receptor 3
Alexopoulou, L., Holt, A. C., Medzhitov, R., & Flavell, R. A. (2001) · Nature · doi:10.1038/35099560 · Cited by 6,129 · see citing works
Toll-like receptor control of the adaptive immune responses
Iwasaki, A., & Medzhitov, R. M. (2004) · Nature Immunology · doi:10.1038/ni1112 · Cited by 4,166 · see citing works
Yoneyama, M., Kikuchi, M., Natsukawa, T., Shinobu, N., Imaizumi, T., Miyagishi, M., Taira, K., Akira, S., & Fujita, T. (2004) · Nature Immunology · doi:10.1038/ni1087 · Cited by 3,935 · see citing works
Innate antiviral responses by means of TLR7-mediated recognition of single-stranded RNA
Diebold, S. S., Kaisho, T., Hemmi, H., Akira, S., & Reis e Sousa, C. (2004) · Science · doi:10.1126/science.1093616 · Cited by 3,444 · see citing works
Seth, R. B., Sun, L., Ea, C.-K., & Chen, Z. J. (2005) · Cell · doi:10.1016/j.cell.2005.08.012 · Cited by 3,329 · see citing works
Role of Adaptor TRIF in the MyD88-Independent Toll-Like Receptor Signaling Pathway
Yamamoto, M., Sato, S., Hemmi, H., Hoshino, K., Kaisho, T., Sanjo, H., Takeuchi, O., Sugiyama, M., Okabe, M., Takeda, K., et al. (2003) · Science · doi:10.1126/science.1087262 · Cited by 3,244 · see citing works
IKKε and TBK1 are essential components of the IRF3 signaling pathway
Fitzgerald, K. A., McWhirter, S. M., Faia, K. L., Rowe, D. C., Latz, E., Golenbock, D. T., Coyle, A. J., Liao, S.-M., & Maniatis, T. (2003) · Nature Immunology · doi:10.1038/ni921 · Cited by 2,680 · see citing works
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 · see citing works
Self-citationCardif 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 · see citing works
IRF-7 is the master regulator of type-I interferon-dependent immune responses
Honda, K., Yanai, H., Negishi, H., Asagiri, M., Sato, M., Mizutani, T., Shimada, N., Ohba, Y., Takaoka, A., Yoshida, N., et al. (2005) · Nature · doi:10.1038/nature03464 · Cited by 2,229 · see citing works
VISA Is an Adapter Protein Required for Virus-Triggered IFN-β Signaling
Xu, L., Wang, Y., Han, K.-J., Li, L., Zhai, Z., & Shu, H. (2005) · Molecular Cell · doi:10.1016/j.molcel.2005.08.014 · Cited by 1,849 · see citing works
Yoneyama, M., Kikuchi, M., Matsumoto, K., Imaizumi, T., Miyagishi, M., Taira, K., Foy, E. M., Loo, Y., Gale, M., Akira, S., et al. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.5.2851 · Cited by 1,691 · see citing works
Triggering the Interferon Antiviral Response Through an IKK-Related Pathway
Sharma, S., tenOever, B. R., Grandvaux, N., Zhou, G., Lin, R., & Hiscott, J. B. (2003) · Science · doi:10.1126/science.1081315 · Cited by 1,664 · see citing works
Inferences, questions and possibilities in Toll-like receptor signalling
Beutler, B. (2004) · Nature · doi:10.1038/nature02761 · Cited by 1,458 · see citing works
Viruses and interferon: a fight for supremacy
Katze, M. G., He, Y., & Gale, M. (2002) · Nature Reviews Immunology · doi:10.1038/nri888 · Cited by 1,419 · see citing works
Cell Type-Specific Involvement of RIG-I in Antiviral Response
Kato, H., Sato, S., Yoneyama, M., Yamamoto, M., Uematsu, S., Matsui, K., Tsujimura, T., Takeda, K., Fujita, T., Takeuchi, O., et al. (2005) · Immunity · doi:10.1016/j.immuni.2005.04.010 · Cited by 1,368 · see citing works
Sato, M., Suemori, H., Hata, N., Asagiri, M., Ogasawara, K., Nakao, K., Nakaya, T., Katsuki, M., Noguchi, S., Tanaka, N., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00053-4 · Cited by 1,342 · see citing works
Andrejeva, J., Childs, K., Young, D. F., Carlos, T. S., Stock, N., Goodbourn, S., & Randall, R. E. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0407639101 · Cited by 990 · see citing works
Kang, D.-C., Gopalkrishnan, R. V., Wu, Q., Jankowsky, E., Pyle, A. M., & Fisher, P. B. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.022637199 · Cited by 651 · see citing works
Rothenfußer, S., Goutagny, N., DiPerna, G., Gong, M., Monks, B. G., Schoenemeyer, A., Yamamoto, M., Akira, S., & Fitzgerald, K. A. (2005) · The Journal of Immunology · doi:10.4049/jimmunol.175.8.5260 · Cited by 645 · see citing works
Hemmi, H., Takeuchi, O., Sato, S., Yamamoto, M., Kaisho, T., Sanjo, H., Kawai, T., Hoshino, K., Takeda, K., & Akira, S. (2004) · The Journal of Experimental Medicine · doi:10.1084/jem.20040520 · Cited by 576 · see citing works
Differential involvement of IFN- in Toll-like receptor-stimulated dendritic cell activation
Hoshino, K., Kaisho, T., Iwabe, T., Takeuchi, O., & Akira, S. (2002) · International Immunology · doi:10.1093/intimm/dxf089 · Cited by 282 · see citing works
Chang, T.-H., Liao, C., & Lin, Y. (2005) · Microbes and Infection · doi:10.1016/j.micinf.2005.06.014 · Cited by 235 · see citing works
Melchjorsen, J., Jensen, S. B., Malmgaard, L., Rasmussen, S. B., Weber, F., Bowie, A., Matikainen, S., & Paludan, S. R. (2005) · Journal of Virology · doi:10.1128/jvi.79.20.12944-12951.2005 · Cited by 192 · see citing works
Nuclear Localization of Japanese Encephalitis Virus Core Protein Enhances Viral Replication
Mori, Y., Okabayashi, T., Yamashita, T., Zhao, Z., Wakita, T., Yasui, K., Hasebe, F., Tadano, M., Konishi, E., Moriishi, K., et al. (2005) · Journal of Virology · doi:10.1128/jvi.79.6.3448-3458.2005 · Cited by 144 · see citing works
Kovacsovics, M., Martinon, F., Micheau, O., Bodmer, J.-L., Hofmann, K., & Tschopp, J. (2002) · Current Biology · doi:10.1016/s0960-9822(02)00842-4 · Cited by 136 · see citing works
Kato, A., Grogan, C. C., Moyer, S. A., Sugahara, F., Sakaguchi, T., Kubota, T., Otsuki, N., Kohase, M., Tashiro, M., & Nagai, Y. (2004) · Journal of Virology · doi:10.1128/jvi.78.14.7443-7454.2004 · Cited by 49 · see citing works
Flagged first, then by citations
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Takeuchi, O., & Akira, S. (2010) · Cell · doi:10.1016/j.cell.2010.01.022 · Cited by 8,895 · see citing works
STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling
Ishikawa, H., & Barber, G. N. (2008) · Nature · doi:10.1038/nature07317 · Cited by 3,576 · see citing works
Pathogen Recognition and Inflammatory Signaling in Innate Immune Defenses
Mogensen, T. H. (2009) · Clinical Microbiology Reviews · doi:10.1128/cmr.00046-08 · Cited by 3,122 · see citing works
STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity
Ishikawa, H., Ma, Z., & Barber, G. N. (2009) · Nature · doi:10.1038/nature08476 · Cited by 2,759 · see citing works
5'-Triphosphate RNA Is the Ligand for RIG-I
Hornung, V., Ellegast, J., Kim, S., Brzózka, K., Jung, A., Kato, H., Poeck, H., Akira, S., Conzelmann, K.-K., Schlee, M., et al. (2006) · Science · doi:10.1126/science.1132505 · Cited by 2,474 · see citing works
Recognition of microorganisms and activation of the immune response
Medzhitov, R. (2007) · Nature · doi:10.1038/nature06246 · Cited by 2,862 · see citing works
Signaling to NF-κB by Toll-like receptors
Kawai, T., & Akira, S. (2007) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2007.09.002 · Cited by 2,395 · see citing works
Pathogen Recognition by the Innate Immune System
Kumar, H., Kawai, T., & Akira, S. (2011) · International Reviews of Immunology · doi:10.3109/08830185.2010.529976 · Cited by 2,264 · see citing works
Toll-like Receptors and the Control of Immunity
Fitzgerald, K. A., & Kagan, J. C. (2020) · Cell · doi:10.1016/j.cell.2020.02.041 · Cited by 2,168 · see citing works
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 · see citing works
Vaccine Adjuvants: Putting Innate Immunity to Work
Coffman, R. L., Sher, A., & Seder, R. A. (2010) · Immunity · doi:10.1016/j.immuni.2010.10.002 · Cited by 1,927 · see citing works
Immune Signaling by RIG-I-like Receptors
Loo, Y.-M., & Gale, M. (2011) · Immunity · doi:10.1016/j.immuni.2011.05.003 · Cited by 1,875 · see citing works
Pattern recognition receptors in health and diseases
Li, D., & Wu, M. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00687-0 · Cited by 1,830 · see citing works
Karki, R., Sharma, B. R., Tuladhar, S., Williams, E. P., Zalduondo, L., Samir, P., Zheng, M., Sundaram, B., Banoth, B., Malireddi, R. K. S., et al. (2021) · Cell · doi:10.1016/j.cell.2020.11.025 · Cited by 1,734 · see citing works
DAI (DLM-1/ZBP1) is a cytosolic DNA sensor and an activator of innate immune response
Takaoka, A., Wang, Z., Choi, M. K., Yanai, H., Negishi, H., Ban, T., Lu, Y., Miyagishi, M., Kodama, T., Honda, K., et al. (2007) · Nature · doi:10.1038/nature06013 · Cited by 1,704 · see citing works
RIG-I-like receptors: their regulation and roles in RNA sensing
Rehwinkel, J., & Gack, M. U. (2020) · Nature reviews. Immunology · doi:10.1038/s41577-020-0288-3 · Cited by 1,703 · see citing works
Honda, K., & Taniguchi, T. (2006) · Nature reviews. Immunology · doi:10.1038/nri1900 · Cited by 1,676 · see citing works
The roles of TLRs, RLRs and NLRs in pathogen recognition
Kawai, T., & Akira, S. (2009) · International Immunology · doi:10.1093/intimm/dxp017 · Cited by 1,666 · see citing works
Kato, H., Takeuchi, O., Mikamo, E., Hirai, R., Kawai, T., Matsushita, K., Hiiragi, A., Dermody, T. S., Fujita, T., & Akira, S. (2008) · The Journal of Experimental Medicine · doi:10.1084/jem.20080091 · Cited by 1,590 · see citing works
Randall, R. E., & Goodbourn, S. (2007) · Journal of General Virology · doi:10.1099/vir.0.83391-0 · Cited by 1,559 · see citing works
The Adaptor Protein MITA Links Virus-Sensing Receptors to IRF3 Transcription Factor Activation
Zhong, B., Yang, Y., Li, S., Wang, Y., Li, Y., Diao, F., Lei, C., He, X., Zhang, L., Tien, P., et al. (2008) · Immunity · doi:10.1016/j.immuni.2008.09.003 · Cited by 1,513 · see citing works
Robust associations of four new chromosome regions from genome-wide analyses of type 1 diabetes
Finland, G. O. T. 1. D. I., Todd, J. A., the Wellcome Trust Case Control Consortium, Walker, N. M., Cooper, J. D., Smyth, D. J., Downes, K., Plagnol, V., Bailey, R., Nejentsev, S., et al. (2007) · Nature Genetics · doi:10.1038/ng2068 · Cited by 1,456 · see citing works
Type I Inteferon Gene Induction by the Interferon Regulatory Factor Family of Transcription Factors
Honda, K., Takaoka, A., & Taniguchi, T. (2006) · Immunity · doi:10.1016/j.immuni.2006.08.009 · Cited by 1,386 · see citing works
Cooperation of Toll-like receptor signals in innate immune defence
Trinchieri, G., & Sher, A. (2007) · Nature reviews. Immunology · doi:10.1038/nri2038 · Cited by 1,357 · see citing works
Interferon-stimulated genes and their antiviral effector functions
Schoggins, J. W., & Rice, C. M. (2011) · Current Opinion in Virology · doi:10.1016/j.coviro.2011.10.008 · Cited by 1,296 · see citing works
Hou, F., Sun, L., Zheng, H., Skaug, B. A., Jiang, Q., & Chen, Z. J. (2011) · Cell · doi:10.1016/j.cell.2011.06.041 · Cited by 1,274 · see citing works
Regulation and Function of IKK and IKK-Related Kinases
Häcker, H., & Karin, M. (2006) · Science s STKE · doi:10.1126/stke.3572006re13 · Cited by 1,269 · see citing works
The IRF Family Transcription Factors in Immunity and Oncogenesis
Tamura, T., Yanai, H., Savitsky, D., & Taniguchi, T. (2008) · Annual Review of Immunology · doi:10.1146/annurev.immunol.26.021607.090400 · Cited by 1,259 · see citing works
TRAM couples endocytosis of Toll-like receptor 4 to the induction of interferon-β
Kagan, J. C., Su, T., Horng, T., Chow, A. Y., Akira, S., & Medzhitov, R. M. (2008) · Nature Immunology · doi:10.1038/ni1569 · Cited by 1,256 · see citing works
Innate immunity to virus infection
Takeuchi, O., & Akira, S. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00737.x · Cited by 1,231 · see citing works
Intracellular pattern recognition receptors in the host response
Meylan, E., Tschopp, J., & Karin, M. (2006) · Nature · doi:10.1038/nature04946 · Cited by 1,196 · see citing works
Type I Interferons in Host Defense
Stetson, D. B., & Medzhitov, R. M. (2006) · Immunity · doi:10.1016/j.immuni.2006.08.007 · Cited by 1,194 · see citing works
Innate Immune Sensing and Signaling of Cytosolic Nucleic Acids
Wu, J., & Chen, Z. J. (2014) · Annual Review of Immunology · doi:10.1146/annurev-immunol-032713-120156 · Cited by 1,179 · see citing works
Hayden, M. S., West, A. P., & Ghosh, S. (2006) · Oncogene · doi:10.1038/sj.onc.1209943 · Cited by 1,178 · see citing works
Toll-like receptors and innate immunity
Kumar, H., Kawai, T., & Akira, S. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.08.062 · Cited by 1,171 · see citing works
Interferons at age 50: past, current and future impact on biomedicine
Borden, E. C., Sen, G. C., Uze, G., Silverman, R. H., Ransohoff, R. M., Foster, G. R., & Stark, G. R. (2007) · Nature Reviews Drug Discovery · doi:10.1038/nrd2422 · Cited by 1,154 · see citing works
Hayden, M. S., & Ghosh, S. (2011) · Cell Research · doi:10.1038/cr.2011.13 · Cited by 1,120 · see citing works
Allen, I. C., Scull, M. A., Moore, C. B., Holl, E. K., McElvania-TeKippe, E., Taxman, D. J., Guthrie, E. H., Pickles, R. J., & Ting, J. P.-Y. (2009) · Immunity · doi:10.1016/j.immuni.2009.02.005 · Cited by 1,113 · see citing works
Distinct RIG-I and MDA5 Signaling by RNA Viruses in Innate Immunity
Loo, Y.-M., Fornek, J., Crochet, N., Bajwa, G., Perwitasari, O., Martinez-Sobrido, L., Akira, S., Gill, M. A., García-Sastre, A., Katze, M. G., et al. (2008) · Journal of Virology · doi:10.1128/jvi.01080-07 · Cited by 1,071 · see citing works
Toll‐like Receptor and RIG‐1‐like Receptor Signaling
Kawai, T., & Akira, S. (2008) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1443.020 · Cited by 985 · see citing works
Nejentsev, S., Walker, N., Riches, D., Egholm, M., & Todd, J. A. (2009) · Science · doi:10.1126/science.1167728 · Cited by 958 · see citing works
Evasion of Type I Interferon by SARS-CoV-2
Xia, H., Cao, Z., Xie, X., Zhang, X., Chen, J. Y.-C., Wang, H., Menachery, V. D., Rajsbaum, R., & Shi, P.-Y. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.108234 · Cited by 957 · see citing works
Aberrant innate immune response in lethal infection of macaques with the 1918 influenza virus.
Kobasa, D., Jones, S. M., Shinya, K., Kash, J. C., Copps, J., Ebihara, H., Hatta, Y., Hyun Kim, J., Halfmann, P., Hatta, M., et al. (2007) · Nature · doi:10.1038/nature05495 · Cited by 934 · see citing works
Type I Interferon Inhibits Interleukin-1 Production and Inflammasome Activation
Guarda, G., Braun, M., Staehli, F., Tardivel, A., Mattmann, C., Förster, I., Farlik, M., Decker, T., Pasquier, R. D., Romero, P. J., et al. (2011) · Immunity · doi:10.1016/j.immuni.2011.02.006 · Cited by 924 · see citing works
Dendritic cell-based immunotherapy
Sabado, R. L., Balan, S., & Bhardwaj, N. (2016) · Cell Research · doi:10.1038/cr.2016.157 · Cited by 926 · see citing works
Sequence- and target-independent angiogenesis suppression by siRNA via TLR3
Kleinman, M. E., Yamada, K., Takeda, A., Chandrasekaran, V., Nozaki, M., Baffi, J., Albuquerque, R., Yamasaki, S., Itaya, M., Pan, Y., et al. (2008) · Nature · doi:10.1038/nature06765 · Cited by 931 · see citing works
Ablasser, A., Bauernfeind, F. G., Hartmann, G., Latz, E., Fitzgerald, K. A., & Hornung, V. (2009) · Nature Immunology · doi:10.1038/ni.1779 · Cited by 892 · see citing works
The helicase DDX41 senses intracellular DNA mediated by the adaptor STING in dendritic cells
Zhang, Z., Yuan, B., Bao, M., Lu, N., Kim, T., & Liu, Y. (2011) · Nature Immunology · doi:10.1038/ni.2091 · Cited by 874 · see citing works
Sun, W., Li, Y., Chen, L., Chen, H., You, F., Zhou, X., Zhou, Y., Zhai, Z., Chen, D., & Jiang, Z. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900850106 · Cited by 862 · see citing works
Autophagy-Dependent Viral Recognition by Plasmacytoid Dendritic Cells
Lee, H. K., Lund, J. M., Ramanathan, B., Mizushima, N., & Iwasaki, A. (2007) · Science · doi:10.1126/science.1136880 · Cited by 865 · see citing works
Goubau, D., Deddouche, S., & Sousa, C. R. E. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.007 · Cited by 847 · see citing works
Peroxisomes are signaling platforms for antiviral innate immunity
Dixit, E., Boulant, S., Zhang, Y.-J., Lee, A. S., Odendall, C., Shum, B. O. V., Hacohen, N., Chen, Z.-J. J., Whelan, S. P. J., Fransen, M., et al. (2010) · Cell · doi:10.1016/j.cell.2010.04.018 · Cited by 848 · see citing works
Type 1 Diabetes: Etiology, Immunology, and Therapeutic Strategies
Van Belle, T. L., Coppieters, K. T., & Von Herrath, M. G. (2011) · Physiological Reviews · doi:10.1152/physrev.00003.2010 · Cited by 1,022 · see citing works
Schlee, M., Roth, A. H. F. J., Hornung, V., Hagmann, C. A., Wimmenauer, V., Barchet, W., Coch, C., Janke, M., Mihailovic, A., Wardle, G. S., et al. (2009) · Immunity · doi:10.1016/j.immuni.2009.05.008 · Cited by 792 · see citing works
Biology and pathogenesis of chikungunya virus
Schwartz, O., & Albert, M. L. (2010) · Nature Reviews Microbiology · doi:10.1038/nrmicro2368 · Cited by 782 · see citing works
TLRs, NLRs and RLRs: a trinity of pathogen sensors that co-operate in innate immunity
Creagh, E. M., & O’Neill, L. A. J. (2006) · Trends in Immunology · doi:10.1016/j.it.2006.06.003 · Cited by 762 · see citing works
Signaling Pathways Downstream of Pattern-Recognition Receptors and Their Cross Talk
Lee, M. S., & Kim, Y. (2007) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.76.060605.122847 · Cited by 756 · see citing works
Activation of innate immune antiviral responses by Nod2
Sabbah, A., Chang, T. H., Harnack, R., Frohlich, V. C., Tominaga, K., Dube, P. H., Xiang, Y., & Bose, S. (2009) · Nature Immunology · doi:10.1038/ni.1782 · Cited by 754 · see citing works
Respiratory Viral Infections in Infants: Causes, Clinical Symptoms, Virology, and Immunology
Tregoning, J. S., & Schwarze, J. (2010) · Clinical Microbiology Reviews · doi:10.1128/cmr.00032-09 · Cited by 746 · see citing works
Viral evasion and subversion of pattern-recognition receptor signalling
Bowie, A., & Unterholzner, L. (2008) · Nature reviews. Immunology · doi:10.1038/nri2436 · Cited by 746 · see citing works
Regulation of innate antiviral defenses through a shared repressor domain in RIG-I and LGP2
Saito, T., Hirai, R., Loo, Y., Owen, D. M., Johnson, C., Sinha, S. C., Akira, S., Fujita, T., & Gale, M. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0606699104 · Cited by 743 · see citing works
Hou, J., Wang, P., Lin, L., Liu, X., Ma, F., An, H., Wang, Z., & Cao, X. (2009) · The Journal of Immunology · doi:10.4049/jimmunol.0900707 · Cited by 739 · see citing works
Innate immunity induced by composition-dependent RIG-I recognition of hepatitis C virus RNA
Saito, T., Owen, D. M., Jiang, F., Marcotrigiano, J., & Gale, M. (2008) · Nature · doi:10.1038/nature07106 · Cited by 745 · see citing works
Recognition and Signaling by Toll-Like Receptors
West, A. P., Koblansky, A. A., & Ghosh, S. (2006) · Annual Review of Cell and Developmental Biology · doi:10.1146/annurev.cellbio.21.122303.115827 · Cited by 718 · see citing works
Toll‐like receptors and adaptor molecules in liver disease: Update†
Seki, E., & Brenner, D. A. (2008) · Hepatology · doi:10.1002/hep.22306 · Cited by 722 · see citing works
LGP2 is a positive regulator of RIG-I– and MDA5-mediated antiviral responses
Satoh, T., Kato, H., Kumagai, Y., Yoneyama, M., Sato, S., Matsushita, K., Tsujimura, T., Fujita, T., Akira, S., & Takeuchi, O. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0912986107 · Cited by 697 · see citing works
Pichlmair, A., & Sousa, C. R. E. (2007) · Immunity · doi:10.1016/j.immuni.2007.08.012 · Cited by 690 · see citing works
Structural Basis for the Activation of Innate Immune Pattern-Recognition Receptor RIG-I by Viral RNA
Kowalinski, E., Lunardi, T., McCarthy, A. A., Louber, J., Brunel, J., Grigorov, B., Gerlier, D., & Cusack, S. (2011) · Cell · doi:10.1016/j.cell.2011.09.039 · Cited by 689 · see citing works
HMGB proteins function as universal sentinels for nucleic-acid-mediated innate immune responses
Yanai, H., Ban, T., Wang, Z., Choi, M. K., Kawamura, T., Negishi, H., Nakasato, M., Lu, Y., Hangai, S., Koshiba, R., et al. (2009) · Nature · doi:10.1038/nature08512 · Cited by 683 · see citing works
TLR3: Interferon induction by double-stranded RNA including poly(I:C)☆
MATSUMOTO, M., & Seya, T. (2008) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2007.11.005 · Cited by 690 · see citing works
Immune defence against Candida fungal infections
Netea, M. G., Joosten, L. A. B., van der Meer, J. W. M., Kullberg, B.-J., & van de Veerdonk, F. L. (2015) · Nature Reviews Immunology · doi:10.1038/nri3897 · Cited by 642 · see citing works
Cao, X. (2015) · Nature reviews. Immunology · doi:10.1038/nri.2015.8 · Cited by 661 · see citing works
Longhi, M. P., Trumpfheller, C., Idoyaga, J., Caskey, M. F., de Matos, I. G., Kluger, C., Salazar, A. Μ., Colonna, M., & Steinman, R. M. (2009) · The Journal of Experimental Medicine · doi:10.1084/jem.20090247 · Cited by 663 · see citing works
The Role of Astrocytes in CNS Inflammation
Giovannoni, F., & Quintana, F. J. (2020) · Trends in Immunology · doi:10.1016/j.it.2020.07.007 · Cited by 651 · see citing works
The airway epithelium: soldier in the fight against respiratory viruses
Vareille, M., Kieninger, E., Edwards, M. R., & Regamey, N. (2011) · Clinical Microbiology Reviews · doi:10.1128/cmr.00014-10 · Cited by 655 · see citing works
Small self-RNA generated by RNase L amplifies antiviral innate immunity
Malathi, K., Dong, B., Gale, M., & Silverman, R. H. (2007) · Nature · doi:10.1038/nature06042 · Cited by 636 · see citing works
The perfect mix: recent progress in adjuvant research
Guy, B. (2007) · Nature Reviews Microbiology · doi:10.1038/nrmicro1681 · Cited by 621 · see citing works
Developing mRNA-vaccine technologies
Schlake, T., Thess, A., Fotin-Mleczek, M., & Kallen, K.-J. (2012) · RNA Biology · doi:10.4161/rna.22269 · Cited by 622 · see citing works
Macrophage activation by endogenous danger signals
Zhang, X., & Mosser, D. (2007) · The Journal of Pathology · doi:10.1002/path.2284 · Cited by 612 · see citing works
Hansdóttir, S., Monick, M. M., Hinde, S. L., Lovan, N., Look, D. C., & Hunninghake, G. W. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.181.10.7090 · Cited by 609 · see citing works
The Specific and Essential Role of MAVS in Antiviral Innate Immune Responses
Sun, Q., Sun, L., Liu, H.-H., Chen, X., Seth, R. B., Forman, J., & Chen, Z. J. (2006) · Immunity · doi:10.1016/j.immuni.2006.04.004 · Cited by 604 · see citing works
Jensen, S., & Thomsen, A. R. (2012) · Journal of Virology · doi:10.1128/jvi.05738-11 · Cited by 604 · see citing works
DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.036 · Cited by 592 · see citing works
Sato, S., Hoshino, K., Satoh, T., Fujita, T., Kawakami, Y., Fujita, T., & Kuwana, M. (2009) · Arthritis & Rheumatism · doi:10.1002/art.24621 · Cited by 601 · see citing works
Discriminating self from non-self in nucleic acid sensing
Schlee, M., & Hartmann, G. (2016) · Nature reviews. Immunology · doi:10.1038/nri.2016.78 · Cited by 587 · see citing works
RNA recognition and signal transduction by RIG‐I‐like receptors
Yoneyama, M., & Fujita, T. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00727.x · Cited by 594 · see citing works
Tetherin Inhibits HIV-1 Release by Directly Tethering Virions to Cells
Pérez-Caballero, D., Zang, T. M., Ebrahimi, A., McNatt, M. W., Gregory, D. A., Johnson, M. C., & Bieniasz, P. D. (2009) · Cell · doi:10.1016/j.cell.2009.08.039 · Cited by 590 · see citing works
Zheng, M., & Kanneganti, T. (2020) · Immunological Reviews · doi:10.1111/imr.12909 · Cited by 591 · see citing works
Pathogen recognition in the innate immune response
Kumar, H., Kawai, T., & Akira, S. (2009) · Biochemical Journal · doi:10.1042/bj20090272 · Cited by 586 · see citing works
RIG-I detects viral genomic RNA during negative-strand RNA virus infection
Rehwinkel, J., Tan, C. P., Goubau, D., Schulz, O., Pichlmair, A., Bier, K., Robb, N., Vreede, F., Barclay, W., Fodor, E., et al. (2010) · Cell · doi:10.1016/j.cell.2010.01.020 · Cited by 585 · see citing works
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 · see citing works
SARS-CoV-2 Disrupts Splicing, Translation, and Protein Trafficking to Suppress Host Defenses
Banerjee, A. K., Blanco, M. R., Bruce, E. A., Honson, D. D., Chen, L. M., Chow, A., Bhat, P., Ollikainen, N., Quinodoz, S. A., Loney, C., et al. (2020) · Cell · doi:10.1016/j.cell.2020.10.004 · Cited by 583 · see citing works
Quantitative proteomics reveals subset-specific viral recognition in dendritic cells
Luber, C. A., Cox, J., Lauterbach, H., Fancke, B., Selbach, M., Tschopp, J., Akira, S., Wiegand, M., Hochrein, H., O'Keeffe, M., et al. (2010) · Immunity · doi:10.1016/j.immuni.2010.01.013 · Cited by 576 · see citing works
Self-citationMibayashi, M., Martínez‐Sobrido, L., Loo, Y., Cardenas, W. B., Gale, M., & García‐Sastre, A. (2006) · Journal of Virology · doi:10.1128/jvi.01265-06 · Cited by 574 · see citing works
Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling
Tal, M. C., Sasai, M., Lee, H. K., Yordy, B., Shadel, G. S., & Iwasaki, A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0807694106 · Cited by 573 · see citing works
MDA5/RIG-I and virus recognition
Takeuchi, O., & Akira, S. (2008) · Current Opinion in Immunology · doi:10.1016/j.coi.2008.01.002 · Cited by 567 · see citing works
Mitochondrial Control of Cellular Life, Stress, and Death
Galluzzi, L., Kepp, O., Trojel‐Hansen, C., & Kroemer, G. (2012) · Circulation Research · doi:10.1161/circresaha.112.268946 · Cited by 545 · see citing works
Yan, N., & Chen, Z. J. (2012) · Nature Immunology · doi:10.1038/ni.2229 · Cited by 535 · see citing works
The Death Domain Superfamily in Intracellular Signaling of Apoptosis and Inflammation
Park, H. H., Lo, Y.-C., Lin, S., Wang, L., Yang, J. K., & Wu, H. (2007) · Annual Review of Immunology · doi:10.1146/annurev.immunol.25.022106.141656 · Cited by 523 · see citing works
Poeck, H., Bscheider, M., Groß, O., Finger, K., Roth, S., Rebsamen, M., Hannesschläger, N., Schlee, M., Rothenfußer, S., Barchet, W., et al. (2009) · Nature Immunology · doi:10.1038/ni.1824 · Cited by 518 · see citing works
- Authors
- Kato, H., Takeuchi, O., Sato, S., Yoneyama, M., Yamamoto, M., Matsui, K., Uematsu, S., Jung, A., Kawai, T., Ishii, K. J., Yamaguchi, O., Otsu, K., Tsujimura, T., Koh, C.-S., Reis e Sousa, C., Matsuura, Y., Fujita, T., & Akira, S.
- Affiliations
- Research Institute for Microbial Diseases, The University of Osaka (JP)
- Japan Science and Technology Agency (JP)
- Kyoto University (JP)
- The University of Osaka (JP)
- Hyogo Medical University (JP)
- Shinshu University (JP)
- Corresponding author
- Akira, Shizuo
- ORCID
- Venue
- Nature
- Published
- 2006-04-09
- Volume
- 441
- Issue
- 7089
- Pages
- 101-105
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2028575270
- Cited by
- 3,888
- References
- 28
- Citations by year
- 2026: 143 · 2025: 156 · 2024: 146 · 2023: 163 · 2022: 176 · 2021: 204 · 2020: 182 · 2019: 169 · 2018: 169 · 2017: 175 · 2016: 169 · 2015: 182 · 2014: 233 · 2013: 218 · 2012: 236
- FWCI
- 88.17
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA regulation and disease
- Keywords
- MDA5, RIG-I, double-stranded RNA recognition, antiviral innate immunity, interferon production, poly(I:C), paramyxovirus, influenza virus, Japanese encephalitis virus, picornavirus, viral susceptibility
- MeSH terms
- DEAD Box Protein 58, Interferon-Induced Helicase, IFIH1, Animals, Encephalitis Virus, Japanese, Encephalomyocarditis virus, Immunity, Innate, RNA Viruses, RNA, Double-Stranded, RNA, Viral, RNA Helicases, Mice, DEAD-box RNA Helicases
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