Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates
Open accessAbstract
Mammalian cells possess mechanisms to detect and defend themselves from invading viruses. In the cytosol, the RIG-I-like receptors (RLRs), RIG-I (retinoic acid-inducible gene I; encoded by DDX58) and MDA5 (melanoma differentiation-associated gene 5; encoded by IFIH1) sense atypical RNAs associated with virus infection. Detection triggers a signalling cascade via the adaptor MAVS that culminates in the production of type I interferons (IFN-α and β; hereafter IFN), which are key antiviral cytokines. RIG-I and MDA5 are activated by distinct viral RNA structures and much evidence indicates that RIG-I responds to RNAs bearing a triphosphate (ppp) moiety in conjunction with a blunt-ended, base-paired region at the 5'-end (reviewed in refs 1, 2, 3). Here we show that RIG-I also mediates antiviral responses to RNAs bearing 5'-diphosphates (5'pp). Genomes from mammalian reoviruses with 5'pp termini, 5'pp-RNA isolated from yeast L-A virus, and base-paired 5'pp-RNAs made by in vitro transcription or chemical synthesis, all bind to RIG-I and serve as RIG-I agonists. Furthermore, a RIG-I-dependent response to 5'pp-RNA is essential for controlling reovirus infection in cultured cells and in mice. Thus, the minimal determinant for RIG-I recognition is a base-paired RNA with 5'pp. Such RNAs are found in some viruses but not in uninfected cells, indicating that recognition of 5'pp-RNA, like that of 5'ppp-RNA, acts as a powerful means of self/non-self discrimination by the innate immune system.
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Through recognition of TLR3 in endosomes or retinoic acid-inducible gene I, melanoma differentiation-associated protein 5, and inflammasomes in the cytoplasm, depending on the amount, dsRNAs might overactivate innate immunity and lead to adverse events.
“Through recognition of TLR3 in endosomes or retinoic acid-inducible gene I, melanoma differentiation-associated protein 5, and inflammasomes in the cytoplasm,96, 97, 98, 99 depending on the amount, dsRNAs might overactivate innate immunity and lead to adverse events.”
From COVID-19 mRNA vaccines: Platforms and current developments (2022) · cites this paper as [97]
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Cites
Genome engineering using the CRISPR-Cas9 system
Ran, F. A., Hsu, P. D., Wright, J., Agarwala, V., Scott, D. A., & Zhang, F. (2013) · Nature Protocols · doi:10.1038/nprot.2013.143 · Cited by 11,133 · see citing works
Inaba, K., Inaba, M., Romani, N., Aya, H., Deguchi, M., Ikehara, S., Muramatsu, S., & Steinman, R. M. (1992) · The Journal of Experimental Medicine · doi:10.1084/jem.176.6.1693 · Cited by 3,741 · 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
CGAS produces a 2′-5′-linked cyclic dinucleotide second messenger that activates STING.
Ablasser, A., Goldeck, M., Cavlar, T., Deimling, T., Witte, G., Röhl, I., Hopfner, K.-P., Ludwig, J., & Hornung, V. (2013) · Nature · doi:10.1038/nature12306 · Cited by 1,695 · 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
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
Goubau, D., Deddouche, S., & Sousa, C. R. E. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.007 · Cited by 840 · 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
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
Viral infection switches non-plasmacytoid dendritic cells into high interferon producers
Diebold, S. S., Montoya, M., Unger, H., Alexopoulou, L., Roy, P., Haswell, L. E., Al‐Shamkhani, A., Flavell, R. A., Borrow, P., & Sousa, C. R. E. (2003) · Nature · doi:10.1038/nature01783 · Cited by 582 · see citing works
Conventional and unconventional mechanisms for capping viral mRNA
Decroly, É., Ferrón, F., Lescar, J., & Canard, B. (2011) · Nature Reviews Microbiology · doi:10.1038/nrmicro2675 · Cited by 495 · see citing works
Activation of MDA5 Requires Higher-Order RNA Structures Generated during Virus Infection
Pichlmair, A., Schulz, O., Tan, C.-P., Rehwinkel, J., Kato, H., Takeuchi, O., Akira, S., Way, M., Schiavo, G., & Sousa, C. R. E. (2009) · Journal of Virology · doi:10.1128/jvi.00770-09 · Cited by 469 · see citing works
Structural basis of RNA recognition and activation by innate immune receptor RIG-I
Jiang, F., Ramanathan, A., Miller, M. T., Tang, G., Gale, M., Patel, S. S., & Marcotrigiano, J. (2011) · Nature · doi:10.1038/nature10537 · Cited by 429 · see citing works
Baum, A., Sachidanandam, R., & García‐Sastre, A. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1005077107 · Cited by 424 · see citing works
Structural Insights into RNA Recognition by RIG-I
Luo, D., Ding, S. C., Vela, A., Kohlway, A. S., Lindenbach, B. D., & Pyle, A. M. (2011) · Cell · doi:10.1016/j.cell.2011.09.023 · Cited by 423 · see citing works
5′-triphosphate RNA requires base-paired structures to activate antiviral signaling via RIG-I
Schmidt, A., Schwerd, T., Hamm, W., Hellmuth, J. C., Cui, S., Wenzel, M., Hoffmann, F. S., Michallet, M.-C., Besch, R., Hopfner, K.-P., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0900971106 · Cited by 398 · see citing works
Wang, Y., Ludwig, J., Schuberth, C., Goldeck, M., Schlee, M., Li, H., Juranek, S., Sheng, G., Micura, R., Tuschl, T., et al. (2010) · Nature Structural & Molecular Biology · doi:10.1038/nsmb.1863 · Cited by 256 · see citing works
The Structural Basis of 5′ Triphosphate Double-Stranded RNA Recognition by RIG-I C-Terminal Domain
Lu, C. C., Xu, H., Ranjith-Kumar, C. T., Brooks, M. T., Hou, T. Y., Hu, F., Herr, A. B., Strong, R. K., Kao, C. C., & Li, P. (2010) · Structure · doi:10.1016/j.str.2010.05.007 · Cited by 233 · see citing works
Antibody protects against lethal infection with the neurally spreading reovirus type 3 (Dearing)
Virgin, H. W., Bassel‐Duby, R., Fields, B. N., & Tyler, K. L. (1988) · Journal of Virology · doi:10.1128/jvi.62.12.4594-4604.1988 · Cited by 229 · see citing works
Enzymatic Synthesis of Nucleic Acidlike Polynucleotides
GRUNBERG‐MANAGO, M., Ortiz, P. J., & Ochoa, S. (1955) · Science · doi:10.1126/science.122.3176.907 · Cited by 227 · see citing works
Master sensors of pathogenic RNA – RIG-I like receptors
Schlee, M. (2013) · Immunobiology · doi:10.1016/j.imbio.2013.06.007 · Cited by 216 · see citing works
Barton, E. S., Connolly, J. L., Forrest, J. C., Chappell, J. D., & Dermody, T. S. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m004680200 · Cited by 215 · see citing works
Isolation of Viral Double-Stranded RNAs Using a LiCl Fractionation Procedure
Dı́az-Ruı́z, J. R., & Kaper, J. M. (1978) · Preparative Biochemistry · doi:10.1080/00327487808068215 · Cited by 164 · see citing works
An improved reverse genetics system for mammalian orthoreoviruses
Kobayashi, T., Ooms, L. S., Ikizler, M. R., Chappell, J. D., & Dermody, T. S. (2009) · Virology · doi:10.1016/j.virol.2009.11.037 · Cited by 154 · see citing works
Holm, G. H., Zurney, J., Tumilasci, V. F., Léveillé, S., Danthi, P., Hiscott, J. B., Sherry, B., & Dermody, T. S. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m702112200 · Cited by 113 · see citing works
Defining the functional determinants for RNA surveillance by RIG‐I
Kohlway, A. S., Luo, D., Rawling, D., Ding, S. C., & Pyle, A. M. (2013) · EMBO Reports · doi:10.1038/embor.2013.108 · Cited by 110 · see citing works
Interplay between Innate Immunity and Negative-Strand RNA Viruses: towards a Rational Model
Gerlier, D., & Lyles, D. S. (2011) · Microbiology and Molecular Biology Reviews · doi:10.1128/mmbr.00007-11 · Cited by 100 · see citing works
Cap-snatching mechanism in yeast L-A double-stranded RNA virus
Fujimura, T., & Esteban, R. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1111900108 · Cited by 93 · see citing works
The Thermodynamic Basis for Viral RNA Detection by the RIG-I Innate Immune Sensor
Vela, A., Fedorova, O., Ding, S. C., & Pyle, A. M. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m112.385146 · Cited by 62 · see citing works
Banerjee, A. K., & Shatkin, A. J. (1971) · Journal of Molecular Biology · doi:10.1016/0022-2836(71)90069-6 · Cited by 45 · see citing works
The Reovirus σ1s Protein Is a Determinant of Hematogenous but Not Neural Virus Dissemination in Mice
Boehme, K. W., Frierson, J. M., Konopka, J. L., Kobayashi, T., & Dermody, T. S. (2011) · Journal of Virology · doi:10.1128/jvi.02289-10 · Cited by 39 · see citing works
Efficient Solid‐Phase Synthesis of pppRNA by Using Product‐Specific Labeling
Goldeck, M., Tuschl, T., Hartmann, G., & Ludwig, J. (2014) · Angewandte Chemie International Edition · doi:10.1002/anie.201400672 · Cited by 32 · see citing works
Blocked and Unblocked 5′ Termini in Reovirus Genome RNA
Chow, N.-L., & Shatkin, A. J. (1975) · Journal of Virology · doi:10.1128/jvi.15.5.1057-1064.1975 · Cited by 26 · see citing works
Yeast Double-stranded RNA Virus L-A Deliberately Synthesizes RNA Transcripts with 5′-Diphosphate
Fujimura, T., & Esteban, R. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.138982 · Cited by 21 · see citing works
Isolation of the trinucleotide pppGpCpU from reovirus
Bellamy, A. R., Hole, L. V., & Baguley, B. C. (1970) · Virology · doi:10.1016/0042-6822(70)90284-9 · Cited by 20 · see citing works
Targeting the viral Achilles’ heel: recognition of 5′-triphosphate RNA in innate anti-viral defence
Rehwinkel, J., & Sousa, C. R. E. (2013) · Current Opinion in Microbiology · doi:10.1016/j.mib.2013.04.009 · Cited by 19 · see citing works
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Coronavirus infections and immune responses
Li, G., Fan, Y., Lai, Y., Han, T., Li, Z., Zhou, P., Pan, P., Wang, W., Hu, D., Liu, X., et al. (2020) · Journal of Medical Virology · doi:10.1002/jmv.25685 · Cited by 1,963 · 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
Aicardi–Goutières syndrome and the type I interferonopathies
Crow, Y. J., & Manel, N. (2015) · Nature Reviews Immunology · doi:10.1038/nri3850 · Cited by 925 · see citing works
mRNA capping: biological functions and applications
Ramanathan, A., Robb, G. B., & Chan, S. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw551 · Cited by 892 · see citing works
The delivery of therapeutic oligonucleotides
Juliano, R. L. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw236 · Cited by 863 · see citing works
Activation of cyclic GMP-AMP synthase by self-DNA causes autoimmune diseases
Gao, D., Li, T., Li, X.-D., Chen, X., Li, Q., Wight‐Carter, M., & Chen, Z. J. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1516465112 · Cited by 685 · see citing works
Advances in mRNA Vaccines for Infectious Diseases
Zhang, C., Maruggi, G., Shan, H., & Li, J. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.00594 · Cited by 680 · 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
Decoding type I and III interferon signalling during viral infection
Mesev, E. V., LeDesma, R. A., & Ploss, A. (2019) · Nature Microbiology · doi:10.1038/s41564-019-0421-x · Cited by 538 · see citing works
Host Immune Response to Influenza A Virus Infection
Chen, X., Liu, S., Goraya, M. U., Maarouf, M., Huang, S., & Chen, J. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2018.00320 · Cited by 461 · see citing works
Viral evasion of intracellular DNA and RNA sensing
Chan, Y., & Gack, M. U. (2016) · Nature Reviews Microbiology · doi:10.1038/nrmicro.2016.45 · Cited by 451 · see citing works
Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids
Tan, J. X., Sun, L., Chen, J., & Chen, Z. J. (2018) · Annual Review of Microbiology · doi:10.1146/annurev-micro-102215-095605 · Cited by 437 · see citing works
Cell death and immunity in cancer: From danger signals to mimicry of pathogen defense responses
Garg, A. D., & Agostinis, P. (2017) · Immunological Reviews · doi:10.1111/imr.12574 · Cited by 448 · see citing works
Cellular origins of dsRNA, their recognition and consequences
Chen, Y. G., & Hur, S. (2021) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00430-1 · Cited by 430 · see citing works
Regulation of RIG-I-like receptor-mediated signaling: interaction between host and viral factors
Onomoto, K., Onoguchi, K., & Yoneyama, M. (2021) · Cellular and Molecular Immunology · doi:10.1038/s41423-020-00602-7 · Cited by 432 · see citing works
RIG-I in RNA virus recognition
Kell, A. M., & Gale, M. (2015) · Virology · doi:10.1016/j.virol.2015.02.017 · Cited by 424 · see citing works
RIG-I and Other RNA Sensors in Antiviral Immunity
Chow, K. T., Gale, M., & Loo, Y. (2018) · Annual Review of Immunology · doi:10.1146/annurev-immunol-042617-053309 · Cited by 429 · see citing works
Viral RNA detection by RIG-I-like receptors
Yoneyama, M., Onomoto, K., Jogi, M., Akaboshi, T., & Fujita, T. (2015) · Current Opinion in Immunology · doi:10.1016/j.coi.2014.12.012 · Cited by 422 · see citing works
Interferons and viruses: an evolutionary arms race of molecular interactions
Hoffmann, H.-H., Schneider, W. M., & Rice, C. M. (2015) · Trends in Immunology · doi:10.1016/j.it.2015.01.004 · Cited by 408 · see citing works
Wicherska‐Pawłowska, K., Wróbel, T., & Rybka, J. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222413397 · Cited by 412 · see citing works
Comparative Structure and Function Analysis of the RIG-I-Like Receptors: RIG-I and MDA5
Brisse, M. E., & Ly, H. (2019) · Frontiers in Immunology · doi:10.3389/fimmu.2019.01586 · Cited by 361 · see citing works
Therapeutic Oligonucleotides: State of the Art
Smith, C. I. E., & Zain, R. (2018) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010818-021050 · Cited by 327 · see citing works
A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation
Dias, A. G., Sampaio, N. G., & Rehwinkel, J. (2018) · Trends in Microbiology · doi:10.1016/j.tim.2018.08.007 · Cited by 309 · see citing works
Schuberth-Wagner, C., Ludwig, J., Bruder, A. K., Herzner, A., Zillinger, T., Goldeck, M., Schmidt, T., Schmid-Burgk, J. L., Kerber, R., Wolter, S., et al. (2015) · Immunity · doi:10.1016/j.immuni.2015.06.015 · Cited by 311 · see citing works
COVID-19 mRNA vaccines: Platforms and current developments
Szabó, G. T., Mahiny, A. J., & Vlatkovic, I. (2022) · Molecular Therapy · doi:10.1016/j.ymthe.2022.02.016 · Cited by 308 · see citing works
Self-Recognition of an Inducible Host lncRNA by RIG-I Feedback Restricts Innate Immune Response
Jiang, M., Zhang, S., Yang, Z., Lin, H., Zhu, J., Liu, L., Wang, W., Liu, S., Liu, W., Ma, Y., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.064 · Cited by 301 · see citing works
Hartmann, G. (2017) · Advances in Immunology · doi:10.1016/bs.ai.2016.11.001 · Cited by 285 · see citing works
Interaction of SARS and MERS Coronaviruses with the Antiviral Interferon Response
Kindler, E., Thiel, V., & Weber, F. (2016) · Advances in virus research · doi:10.1016/bs.aivir.2016.08.006 · Cited by 292 · see citing works
Barnett, K. C., Coronas-Serna, J. M., Zhou, W., Ernandes, M. J., Cao, A., Kranzusch, P. J., & Kagan, J. C. (2019) · Cell · doi:10.1016/j.cell.2019.01.049 · Cited by 268 · see citing works
Vaidyanathan, S., Azizian, K. T., Haque, A. K. M. A., Henderson, J. M., Hendel, A., Shore, S., Antony, J. S., Hogrefe, R. I., Kormann, M. S. D., Porteus, M. H., et al. (2018) · Molecular Therapy Nucleic Acids · doi:10.1016/j.omtn.2018.06.010 · Cited by 262 · see citing works
Viral unmasking of cellular 5S rRNA pseudogene transcripts induces RIG-I-mediated immunity
Chiang, J. J., Sparrer, K. M. J., van Gent, M., Lässig, C., Huang, T., Osterrieder, N., Hopfner, K., & Gack, M. U. (2017) · Nature Immunology · doi:10.1038/s41590-017-0005-y · Cited by 260 · see citing works
The molecular mechanism of RIG‐I activation and signaling
Thoresen, D., Wang, W., Galls, D., Guo, R., Xu, L., & Pyle, A. M. (2021) · Immunological Reviews · doi:10.1111/imr.13022 · Cited by 238 · see citing works
Induction of Pyroptosis and Its Implications in Cancer Management
Wang, Y., Liu, X., & Zhao, R. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00971 · Cited by 242 · see citing works
Durbin, A. F., Wang, C., Marcotrigiano, J., & Gehrke, L. (2016) · mBio · doi:10.1128/mbio.00833-16 · Cited by 238 · see citing works
The long noncoding RNA Lnczc3h7a promotes a TRIM25-mediated RIG-I antiviral innate immune response
Lin, H., Jiang, M., Liu, L., Yang, Z., Ma, Z., Liu, S., Ma, Y., Zhang, L., & Cao, X. (2019) · Nature Immunology · doi:10.1038/s41590-019-0379-0 · Cited by 224 · see citing works
Innate immune sensing of coronavirus and viral evasion strategies
Kasuga, Y., Zhu, B., Jang, K., & Yoo, J. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00602-1 · Cited by 230 · see citing works
Spliceosome-targeted therapies trigger an antiviral immune response in triple-negative breast cancer
Bowling, E. A., Wang, J. H., Gong, F., Wu, W., Neill, N. J., Kim, I. S., Tyagi, S., Orellana, M. C., Kurley, S. J., Domínguez-Vidaña, R., et al. (2021) · Cell · doi:10.1016/j.cell.2020.12.031 · Cited by 221 · see citing works
Intracellular Nucleic Acid Detection in Autoimmunity
Crowl, J. T., Gray, E. E., Pestal, K., Volkman, H. E., & Stetson, D. B. (2017) · Annual Review of Immunology · doi:10.1146/annurev-immunol-051116-052331 · Cited by 217 · see citing works
Innate immune recognition of DNA: A recent history
Dempsey, A., & Bowie, A. (2015) · Virology · doi:10.1016/j.virol.2015.03.013 · Cited by 216 · see citing works
Lee‐Kirsch, M. A. (2016) · Annual Review of Medicine · doi:10.1146/annurev-med-050715-104506 · Cited by 208 · see citing works
Influenza virus activation of the interferon system
Killip, M. J., Fodor, E., & Randall, R. E. (2015) · Virus Research · doi:10.1016/j.virusres.2015.02.003 · Cited by 196 · see citing works
RIG-I-like receptor regulation in virus infection and immunity
Chan, Y., & Gack, M. U. (2015) · Current Opinion in Virology · doi:10.1016/j.coviro.2015.01.004 · Cited by 196 · see citing works
Function of HNRNPC in breast cancer cells by controlling the dsRNA‐induced interferon response
Wu, Y., Zhao, W., Liu, Y., Tan, X., Li, X., Zou, Q., Xiao, Z., Xu, H., Wang, Y., & Yang, X. (2018) · The EMBO Journal · doi:10.15252/embj.201899017 · Cited by 195 · see citing works
Ubiquitin-Dependent and -Independent Roles of E3 Ligase RIPLET in Innate Immunity
Cadena, C., Ahmad, S., Xavier, A., Willemsen, J., Park, S., Park, J. W., Oh, S.-W., Fujita, T., Hou, F., Binder, M., et al. (2019) · Cell · doi:10.1016/j.cell.2019.03.017 · Cited by 196 · see citing works
Ubiquitination in the antiviral immune response
Davis-Gardner, M. E., & Gack, M. U. (2015) · Virology · doi:10.1016/j.virol.2015.02.033 · Cited by 188 · see citing works
Chen, S. N., Zou, P., & Nie, P. (2017) · Immunology · doi:10.1111/imm.12714 · Cited by 186 · see citing works
Immune Sensing Mechanisms that Discriminate Self from Altered Self and Foreign Nucleic Acids
Bartok, E., & Hartmann, G. (2020) · Immunity · doi:10.1016/j.immuni.2020.06.014 · Cited by 184 · see citing works
Cancer therapies activate RIG-I-like receptor pathway through endogenous non-coding RNAs
Rañoa, D. R. E., Parekh, A. D., Pitroda, S. P., Huang, X., Darga, T. E., Wong, A., Huang, L., Andrade, J., Staley, J. P., Satoh, T., et al. (2016) · Oncotarget · doi:10.18632/oncotarget.8420 · Cited by 184 · see citing works
Therapeutically Active RIG-I Agonist Induces Immunogenic Tumor Cell Killing in Breast Cancers
Elion, D. L., Jacobson, M. E., Hicks, D. J., Rahman, B., Sanchez, V. M., Ericsson, P. I. G., Fedorova, O., Pyle, A. M., Wilson, J. T., & Cook, R. S. (2018) · Cancer Research · doi:10.1158/0008-5472.can-18-0730 · Cited by 178 · see citing works
The Role of RNA Interference (RNAi) in Arbovirus-Vector Interactions
Blair, C. D., & Olson, K. E. (2015) · Viruses · doi:10.3390/v7020820 · Cited by 178 · see citing works
Importance of Nucleic Acid Recognition in Inflammation and Autoimmunity
Barrat, F. J., Elkon, K. B., & Fitzgerald, K. A. (2015) · Annual Review of Medicine · doi:10.1146/annurev-med-052814-023338 · Cited by 162 · see citing works
No Love Lost Between Viruses and Interferons
Fensterl, V., Chattopadhyay, S., & Sen, G. C. (2015) · Annual Review of Virology · doi:10.1146/annurev-virology-100114-055249 · Cited by 162 · see citing works
Type I Interferons as Regulators of Lung Inflammation
Makris, S., Paulsen, M. T., & Johansson, C. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2017.00259 · Cited by 159 · see citing works
Bailey-Elkin, B. A., Knaap, R. C. M., Johnson, G. G. R. J., Dalebout, T. J., Ninaber, D. K., van Kasteren, P. B., Bredenbeek, P. J., Snijder, E. J., Kikkert, M., & Mark, B. L. (2014) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.609644 · Cited by 152 · see citing works
RNA aggregates harness the danger response for potent cancer immunotherapy
Méndez‐Gómez, H. R., DeVries, A., Castillo, P., Roemeling, C. A. V., Qdaisat, S., Stover, B. D., Xie, C., Weidert, F. L., Zhao, C., Moor, R., et al. (2024) · Cell · doi:10.1016/j.cell.2024.04.003 · Cited by 158 · see citing works
Translating nucleic acid-sensing pathways into therapies
Junt, T., & Barchet, W. (2015) · Nature reviews. Immunology · doi:10.1038/nri3875 · Cited by 145 · see citing works
USP38 Inhibits Type I Interferon Signaling by Editing TBK1 Ubiquitination through NLRP4 Signalosome
Lin, M., Zhao, Z., Yang, Z., Meng, Q., Tan, P., Xie, W., Qin, Y., Wang, R., & Cui, J. (2016) · Molecular Cell · doi:10.1016/j.molcel.2016.08.029 · Cited by 145 · see citing works
Distinct and Orchestrated Functions of RNA Sensors in Innate Immunity
Liu, G., & Gack, M. U. (2020) · Immunity · doi:10.1016/j.immuni.2020.03.017 · Cited by 143 · see citing works
Exploiting RIG-I-like receptor pathway for cancer immunotherapy
Jiang, Y., Zhang, H., Wang, J., Chen, J., Guo, Z., Liu, Y., & Hua, H. M. (2023) · Journal of Hematology & Oncology · doi:10.1186/s13045-023-01405-9 · Cited by 143 · see citing works
Chiang, C., Pauli, E.-K., Biryukov, J., Feister, K. F., Meng, M., White, E. A., Münger, K., Howley, P. M., Meyers, C., & Gack, M. U. (2017) · Journal of Virology · doi:10.1128/jvi.01737-17 · Cited by 139 · see citing works
Synthesis of low immunogenicity RNA with high-temperature in vitro transcription
Wu, M. Z., Asahara, H., Tzertzinis, G., & Roy, B. (2020) · RNA · doi:10.1261/rna.073858.119 · Cited by 135 · see citing works
Host and Viral Modulation of RIG-I-Mediated Antiviral Immunity
Liu, Y., Olagnier, D. P., & Lin, R. (2017) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00662 · Cited by 135 · see citing works
van der Veen, A. G., Maillard, P. V., Schmidt, J. M., Lee, S. A., Deddouche, S., Borg, A., Kjær, S., Snijders, A. P., & Sousa, C. R. E. (2018) · The EMBO Journal · doi:10.15252/embj.201797479 · Cited by 135 · see citing works
Hertzog, J., Dias, A. G., Rigby, R. E., Donald, C. L., Mayer, A., Sezgin, E., Song, C., Jin, B., Hublitz, P., Eggeling, C., et al. (2018) · European Journal of Immunology · doi:10.1002/eji.201847483 · Cited by 129 · see citing works
Cross-priming in cancer immunology and immunotherapy
Luri‐Rey, C., Teijeira, Á., Wculek, S. K., de Andrea, C. E., Herrero, C., López‐Janeiro, Á., Rodriguez-Ruiz, M. E., Heras‐Murillo, I., Aggelakopoulou, M., Berraondo, P., et al. (2025) · Nature reviews. Cancer · doi:10.1038/s41568-024-00785-5 · Cited by 143 · see citing works
Mechanism of TRIM25 Catalytic Activation in the Antiviral RIG-I Pathway
Sanchez, J. G., Chiang, J. J., Sparrer, K. M. J., Alam, S. L., Chi, M., Roganowicz, M., Sankaran, B., Gack, M. U., & Pornillos, O. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.06.070 · Cited by 133 · see citing works
Past, Present and Future of Oncolytic Reovirus
Müller, L. M. E., Berkeley, R. A., Barr, T., Ilett, E. J., & Errington‐Mais, F. (2020) · Cancers · doi:10.3390/cancers12113219 · Cited by 129 · see citing works
Slicing and dicing viruses: antiviral RNA interference in mammals
Maillard, P. V., van der Veen, A. G., Poirier, E. Z., & Sousa, C. R. E. (2019) · The EMBO Journal · doi:10.15252/embj.2018100941 · Cited by 128 · see citing works
Wang, Y., Yuan, S., Jia, X., Ge, Y., Ling, T., Nie, M., Lan, X., Chen, S., & Xu, A. (2019) · Nature Cell Biology · doi:10.1038/s41556-019-0416-0 · Cited by 129 · see citing works
LGP2 synergy with MDA5 in RLR-mediated RNA recognition and antiviral signaling
Bruns, A. M., & Horvath, C. M. (2015) · Cytokine · doi:10.1016/j.cyto.2015.02.010 · Cited by 127 · see citing works
Biomedical applications of mRNA nanomedicine
Xiong, Q., Lee, G. Y., Ding, J., Li, W., & Shi, J. (2018) · Nano Research · doi:10.1007/s12274-018-2146-1 · Cited by 125 · see citing works
PRRs are watching you: Localization of innate sensing and signaling regulators
Chow, J., Franz, K. M., & Kagan, J. C. (2015) · Virology · doi:10.1016/j.virol.2015.02.051 · Cited by 120 · see citing works
mRNA therapeutics deliver a hopeful message
Zhong, Z., Cafferty, S. M., Combes, F., Huysmans, H., Temmerman, J. D., Gitsels, A., Vanrompay, D. C. G., Catani, J. P., & Sanders, N. N. (2018) · Nano Today · doi:10.1016/j.nantod.2018.10.005 · Cited by 120 · see citing works
A phosphomimetic-based mechanism of dengue virus to antagonize innate immunity
Chan, Y., & Gack, M. U. (2016) · Nature Immunology · doi:10.1038/ni.3393 · Cited by 120 · see citing works
In vitro–transcribed guide RNAs trigger an innate immune response via the RIG-I pathway
Wienert, B., Shin, J. J., Zelin, E., Pestal, K., & Corn, J. E. (2018) · PLoS Biology · doi:10.1371/journal.pbio.2005840 · Cited by 117 · see citing works
Dicer uses distinct modules for recognizing dsRNA termini
Sinha, N. K., Iwasa, J., Shen, P. S., & Bass, B. (2017) · Science · doi:10.1126/science.aaq0921 · Cited by 115 · see citing works
The Multiples Fates of the Flavivirus RNA Genome During Pathogenesis
Mazeaud, C., Freppel, W., & Chatel‐Chaix, L. (2018) · Frontiers in Genetics · doi:10.3389/fgene.2018.00595 · Cited by 112 · see citing works
Liu, G., Park, H.-S., Pyo, H., Liu, Q., & Zhou, Y. (2015) · Journal of Virology · doi:10.1128/jvi.00232-15 · Cited by 114 · see citing works
Potential role for snoRNAs in PKR activation during metabolic stress
Youssef, O. A., Safran, S. A., Nakamura, T., Nix, D. A., Hotamışlıgil, G. S., & Bass, B. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1424044112 · Cited by 113 · see citing works
mRNA delivery systems for cancer immunotherapy: Lipid nanoparticles and beyond
Sentí, M. E., del Valle, L. G., & Schiffelers, R. M. (2024) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2024.115190 · Cited by 116 · see citing works
LINE1 contributes to autoimmunity through both RIG-I- and MDA5-mediated RNA sensing pathways
Zhao, K., Du, J., Peng, Y., Li, P., Wang, S., Wang, Y., Hou, J., Kang, J., Zheng, W., Hua, S., et al. (2018) · Journal of Autoimmunity · doi:10.1016/j.jaut.2018.02.007 · Cited by 106 · see citing works
Evading innate immunity in nonviral mRNA delivery: don't shoot the messenger.
Devoldere, J., Dewitte, H., De Smedt, S. C., & Remaut, K. (2016) · Drug Discovery Today · doi:10.1016/j.drudis.2015.07.009 · Cited by 112 · see citing works
The molecular mechanisms of signaling by cooperative assembly formation in innate immunity pathways
Vajjhala, P. R., Ve, T., Bentham, A. R., Stacey, K. J., & Kobe, B. (2017) · Molecular Immunology · doi:10.1016/j.molimm.2017.02.012 · Cited by 110 · see citing works
Stimulation of Innate Immunity by Host and Viral RNAs
Streicher, F., & Jouvenet, N. (2019) · Trends in Immunology · doi:10.1016/j.it.2019.10.009 · Cited by 111 · see citing works
Kouwaki, T., Nishimura, T., Wang, G., & Oshiumi, H. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.700926 · Cited by 112 · see citing works
Physiological functions of RIG-I-like receptors
Yoneyama, M., Kato, H., & Fujita, T. (2024) · Immunity · doi:10.1016/j.immuni.2024.03.003 · Cited by 113 · see citing works
A minimal RNA ligand for potent RIG-I activation in living mice
Linehan, M. M., Dickey, T. H., Molinari, E., Fitzgerald, M. E., Potapova, O., Iwasaki, A., & Pyle, A. M. (2018) · Science Advances · doi:10.1126/sciadv.1701854 · Cited by 111 · see citing works
Non-immunotherapy application of LNP-mRNA: Maximizing efficacy and safety
Vlatkovic, I. (2021) · Biomedicines · doi:10.3390/biomedicines9050530 · Cited by 112 · see citing works
Type I Interferons Modulate CD8 + T Cell Immunity to mRNA Vaccines
Beuckelaer, A. D., Grooten, J., & Koker, S. D. (2017) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2017.01.006 · Cited by 109 · see citing works
From COVID-19 to Cancer mRNA Vaccines: Moving From Bench to Clinic in the Vaccine Landscape
Chakraborty, C., Sharma, A. R., Bhattacharya, M., & Lee, S. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2021.679344 · Cited by 111 · see citing works
Zhao, Y., Soh, T. S., Lim, S. P., Chung, K. Y., Swaminathan, K., Vasudevan, S. G., Shi, P., Lescar, J., & Luo, D. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1514978112 · Cited by 109 · see citing works
Intracellular detection of viral nucleic acids
Sparrer, K. M. J., & Gack, M. U. (2015) · Current Opinion in Microbiology · doi:10.1016/j.mib.2015.03.001 · Cited by 105 · see citing works
Signaling Through Nucleic Acid Sensors and Their Roles in Inflammatory Diseases
Okude, H., Ori, D., & Kawai, T. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.625833 · Cited by 103 · see citing works
Stimulating the RIG-I pathway to kill cells in the latent HIV reservoir following viral reactivation
Li, P., Kaiser, P. D., Lampiris, H. W., Kim, P., Yukl, S. A., Havlir, D. V., Greene, W. C., & Wong, J. K. (2016) · Nature Medicine · doi:10.1038/nm.4124 · Cited by 103 · see citing works
Innate Immune Sensing of Influenza A Virus
Malik, G., & Zhou, Y. (2020) · Viruses · doi:10.3390/v12070755 · Cited by 105 · see citing works
Regulation of RIG-I Activation by K63-Linked Polyubiquitination
Okamoto, M., Kouwaki, T., Fukushima, Y., & Oshiumi, H. (2018) · Frontiers in Immunology · doi:10.3389/fimmu.2017.01942 · Cited by 100 · see citing works
Cryo-EM Structures of MDA5-dsRNA Filaments at Different Stages of ATP Hydrolysis
Yu, Q., Qu, K., & Modis, Y. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.10.012 · Cited by 102 · see citing works
Review: Cell Death, Nucleic Acids, and Immunity
Elkon, K. B. (2018) · Arthritis & Rheumatology · doi:10.1002/art.40452 · Cited by 99 · see citing works
Elion, D. L., & Cook, R. S. (2018) · Oncotarget · doi:10.18632/oncotarget.25626 · Cited by 99 · see citing works
ATP hydrolysis by the viral RNA sensor RIG-I prevents unintentional recognition of self-RNA
Lässig, C., Matheisl, S., Sparrer, K. M. J., Mann, C. C. D. O., Moldt, M., Patel, J. R., Goldeck, M., Hartmann, G., García‐Sastre, A., Hornung, V., et al. (2015) · eLife · doi:10.7554/elife.10859 · Cited by 96 · see citing works
- Authors
- Goubau, D., Schlee, M., Deddouche, S., Pruijssers, A. J., Zillinger, T., Goldeck, M., Schuberth, C., Van der Veen, A. G., Fujimura, T., Rehwinkel, J., Iskarpatyoti, J. A., Barchet, W., Ludwig, J., Dermody, T. S., Hartmann, G., & Reis e Sousa, C.
- Affiliations
- Cancer Research UK (GB)
- University Hospital Bonn (DE)
- Vanderbilt University (US)
- Consejo Superior de Investigaciones Científicas (ES)
- Corresponding author
- Goubau, Delphine
- ORCID
- Venue
- Nature
- Published
- 2014-08-10
- Volume
- 514
- Issue
- 7522
- Pages
- 372-375
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC4201573
- OpenAlex
- W2156869719
- Cited by
- 557
- References
- 36
- Citations by year
- 2026: 16 · 2025: 40 · 2024: 43 · 2023: 34 · 2022: 54 · 2021: 56 · 2020: 51 · 2019: 51 · 2018: 62 · 2017: 44 · 2016: 43 · 2015: 55 · 2014: 8
- FWCI
- 22.85
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (submittedVersion)
- Funders
- Cancer Research UK (15689, A3598)
- National Institute of Allergy and Infectious Diseases (R01AI038296, R37AI038296, R01AI050800)
- 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
- RIG-I, antiviral innate immunity, RIG-I-like receptors, MDA5, MAVS, type I interferon, reovirus, L-A virus, viral RNA recognition, self/non-self discrimination, cytosolic RNA sensing, RNA-dependent protein kinase, interferon-stimulated genes, interferon lambda
- MeSH terms
- DEAD Box Protein 58, Animals, Base Sequence, Female, Immunity, Innate, Male, Diphosphates, Reoviridae, RNA, Viral, Genome, Viral, Base Pairing, Mice, DEAD-box RNA Helicases
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