Cited by 557interferon and immune responsesImmune Response and InflammationRNA regulation and disease

The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index.

Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates

Open access

Goubau, Delphine, Schlee, Martin, Deddouche, Safia, Pruijssers, Andrea J., Zillinger, Thomas, Goldeck, Marion, Schuberth, Christine, Van der Veen, Annemarthe G., Fujimura, Tsutomu, Rehwinkel, Jan, Iskarpatyoti, Jason A., Barchet, Winfried, Ludwig, Janos, Dermody, Terence S., Hartmann, Gunther, Reis e Sousa, Caetano·2014·Nature

DOI 10.1038/nature13590PMC PMC4201573

Open this paper in CoChat — free account

Abstract

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.

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

Crossref · 10.1038/nature13590

Cites

36 of 36 references verified0 citation errors · 0 not checkable

Statistics

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.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

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
Generation of large numbers of dendritic cells from mouse bone marrow cultures supplemented with granulocyte/macrophage colony-stimulating factor.
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
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
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
Length-dependent recognition of double-stranded ribonucleic acids by retinoic acid–inducible gene-I and melanoma differentiation–associated gene 5
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 1,649
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
Cytosolic Sensing of Viruses
Goubau, D., Deddouche, S., & Sousa, C. R. E. (2013) · Immunity · doi:10.1016/j.immuni.2013.05.007 · Cited by 875
Recognition of 5′ Triphosphate by RIG-I Helicase Requires Short Blunt Double-Stranded RNA as Contained in Panhandle of Negative-Strand Virus
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 814
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
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

Flagged first, then by citations

Show all 36 references

Research works printed but not linked: 1

Dermody, T. S., Sherry, B. & Parker, J. S. L. in Fields Virology 6th edn ( Knipe, D. M. & Howley, P. M. ) 2, 1304–1346 (Wolters Kluwer Health/Lippincott Williams & Wilkins, 2013)

Sorted by citations

Items 301–400 of 556

Closely related reovirus lab strains induce opposite expression of RIG-I/IFN-dependent versus -independent host genes, via mechanisms of slow replication versus polymorphisms in dsRNA binding σ3 respectively
Mohamed, A., Konda, P., Eaton, H. E., Gujar, S. A., Smiley, J. R., & Shmulevitz, M. (2020) · PLoS Pathogens · doi:10.1371/journal.ppat.1008803 · Cited by 22
G3BP1 Inhibition Alleviates Intracellular Nucleic Acid–Induced Autoimmune Responses
Cai, H., Liu, X., Zhang, F., Han, Q., Liu, Z.-S., Xue, W., Guo, Z.-L., Zhao, J., Sun, L.-M., Wang, N., et al. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2001111 · Cited by 22
Biochemical characterization of mRNA capping enzyme from Faustovirus
Chan, S., Molé, C. N., Nye, D. B., Mitchell, L., Dai, N., Buss, J., Kneller, D. W., Whipple, J. M., & Robb, G. B. (2023) · RNA · doi:10.1261/rna.079738.123 · Cited by 23
RNA Nanotherapeutics for the Amelioration of Astroglial Reactivity
Smith, J. A., Braga, A., Verheyen, J., Basilico, S., Bandiera, S., Alfaro‐Cervelló, C., Peruzzotti‐Jametti, L., Shu, D., Haque, F., Guo, P., et al. (2017) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2017.11.008 · Cited by 22
“In mammalian cells, the presence of uncapped 50-triphosphate (or diphosphate) groups on nucleic acids is a known PAMP, recognized in the cytosol by the RIG-I helicase as a probable viral infection and triggering a type I IFN inflammatory response.(91,92) Indeed, siRNA-3WJs retaining their 50-triphosphate groups provok…”
Background
Toll-like Receptors in Viral Encephalitis
Gern, O. L., Mulenge, F., Pavlou, A., Ghita, L., Steffen, I., Stangel, M., & Kalinke, U. (2021) · Viruses · doi:10.3390/v13102065 · Cited by 24
Dynamic Evolution of Avian RNA Virus Sensors: Repeated Loss of RIG-I and RIPLET
Krchlíková, V., Hron, T., Těšičký, M., Li, T., Ungrová, L., Hejnar, J., Vinkler, M., & Elleder, D. (2022) · Viruses · doi:10.3390/v15010003 · Cited by 20
Modifying the antiviral innate immune response by selective writing, erasing, and reading of m6A on viral and cellular RNA
Aufgebauer, C. J., Bland, K. M., & Horner, S. M. (2024) · Cell chemical biology · doi:10.1016/j.chembiol.2023.12.004 · Cited by 24
Host Innate Antiviral Response to Influenza A Virus Infection: From Viral Sensing to Antagonism and Escape
An, W., Lakhina, S., Leong, J., Rawat, K., & Husain, M. (2024) · Pathogens · doi:10.3390/pathogens13070561 · Cited by 23
Differential Delivery of Genomic Double-Stranded RNA Causes Reovirus Strain-Specific Differences in Interferon Regulatory Factor 3 Activation
Stuart, J. D., Holm, G. H., & Boehme, K. W. (2018) · Journal of Virology · doi:10.1128/jvi.01947-17 · Cited by 21
Chikungunya Virus and Zika Virus, Two Different Viruses Examined with a Common Aim: Role of Pattern Recognition Receptors on the Inflammatory Response
Valdés‐López, J. F., Velilla, P. A., & Inchima, S. U. (2019) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2019.0058 · Cited by 21
Myocardial mitochondrial antiviral signaling protein promotes heart Ischemia-reperfusion injury via RIG-I signaling in mice
Kang, Z., Yang, M., Liu, Y., Yang, G., Dong, Y., Zhou, H., Zhang, Z., Li, M., Fan, H., Li, Z., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-60123-7 · Cited by 21
“Previous studies had shown that viral RNA is crucial to activate RIG-I to trigger downstream signaling pathways 20,39,40 .”
A ribosomal RNA fragment with 2′,3′-cyclic phosphate and GTP-binding activity acts as RIG-I ligand
Jung, S., von Thülen, T., Yang, I., Laukemper, V., Rupf, B., Janga, H., Panagiotidis, G., Schoen, A., Nicolai, M., Schulte, L. N., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa739 · Cited by 21
Species-Specific Deamidation of RIG-I Reveals Collaborative Action between Viral and Cellular Deamidases in HSV-1 Lytic Replication
Huang, H., Zhao, J., Wang, T., Zhang, S. J., Zhou, Y., Rao, Y., Qin, C., Liu, Y., Chen, Y., Xia, Z., et al. (2021) · mBio · doi:10.1128/mbio.00115-21 · Cited by 20
DDX50 Is a Viral Restriction Factor That Enhances IRF3 Activation
Pallett, M. A., Lu, Y., & Smith, G. L. (2022) · Viruses · doi:10.3390/v14020316 · Cited by 20
“IRF3 signalling is tightly regulated and is triggered by intracellular cytoplasmic/ endoplasmic detection of viral RNA (dsRNA/5′-ppp/pp-RNA) [3] and DNA by pattern recognition receptors (PRRs) [4].”
Background
Unraveling blunt-end RNA binding and ATPase-driven translocation activities of the RIG-I family helicase LGP2
Lee, K.-Y., Craig, C., & Patel, S. S. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad1106 · Cited by 20
“RIG-I recognizes blunt-ended double-stranded ( ds ) RNAs with a 5 (cid:2) -triphosphate ( 5 (cid:2) ppp ) and 5 (cid:2) PP ( diphosphate ) , while MDA5 recognizes long dsRNA regions ( 4–8 ) .”
Spontaneous activation of a MAVS-dependent antiviral signaling pathway determines high basal interferon-β expression in cardiac myocytes
Rivera-Serrano, E. E., DeAngelis, N., & Sherry, B. (2017) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2017.08.008 · Cited by 19
PACT is required for MDA5-mediated immunoresponses triggered by Cardiovirus infection via interaction with LGP2
Miyamoto, M., & Komuro, A. (2017) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2017.10.048 · Cited by 20
siRNAs and piRNAs collaborate for transposon control in the two-spotted spider mite
Mondal, M., Mansfield, K. P., & Flynt, A. S. (2018) · RNA · doi:10.1261/rna.065839.118 · Cited by 21
Mutual Regulation of RNA Silencing and the IFN Response as an Antiviral Defense System in Mammalian Cells
Takahashi, T., & Ui‐Tei, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21041348 · Cited by 20
Innate and adaptive immune responses against Influenza A Virus: Immune evasion and vaccination strategies
Varghese, P. M., Kishore, U., & Rajkumari, R. (2022) · Immunobiology · doi:10.1016/j.imbio.2022.152279 · Cited by 19
RIG-I immunotherapy overcomes radioresistance in p53-positive malignant melanoma
Lambing, S., Tan, Y. P., Vasileiadou, P., Holdenrieder, S., Müller, P., Hagen, C., Garbe, S., Behrendt, R., Schlee, M., van den Boorn, J. G., et al. (2023) · Journal of Molecular Cell Biology · doi:10.1093/jmcb/mjad001 · Cited by 22
“RIG-I is broadly expressed in nucleated cells, including tumour cells, and can be specifically activated by 5 ′ -tri- or 5 ′ -diphosphorylated, blunt-ended, doublestranded RNA ( dsRNA ) ( Hornung et al., 2006 ; Schlee et al., 2009 ; Goubau et al., 2014 ) .”
Background
The Next Generation of Pattern Recognition Receptor Agonists: Improving Response Rates in Cancer Immunotherapy
O’Donovan, D. H., Mao, Y., & Mele, D. A. (2019) · Current Medicinal Chemistry · doi:10.2174/0929867326666190620103105 · Cited by 19
RNA helicase SKIV2L limits antiviral defense and autoinflammation elicited by the OAS-RNase L pathway
Yang, K., Dong, B., Asthana, A., Silverman, R. H., & Yan, N. (2024) · The EMBO Journal · doi:10.1038/s44318-024-00187-1 · Cited by 18
“3 ’ cyclic phosphate RNA ends produced by metal-ion-independent endoribonucleases can also activate RIG-I (Jung et al, 2020; Shigematsu et al, 2018).”
Influential
LINE-1 ORF1p Mimics Viral Innate Immune Evasion Mechanisms in Pancreatic Ductal Adenocarcinoma
You, E., Patel, B. K., Rojas, A. S., Sun, S., Danaher, P. J., Ho, N. I., Phillips, I. E., Raabe, M. J., Song, Y., Xu, K. H., et al. (2025) · Cancer Discovery · doi:10.1158/2159-8290.cd-24-1317 · Cited by 20
RNF144B negatively regulates antiviral immunity by targeting MDA5 for autophagic degradation
Li, G., Zhang, J., Zhao, Z., Wang, J., Li, J., Xu, W., Cui, Z., Sun, P., Yuan, H., Wang, T., et al. (2024) · EMBO Reports · doi:10.1038/s44319-024-00256-w · Cited by 16
“RIG-I primarily detects viral 5-diphosphate (5 ′ pp) or 5 ′ -triphosphate (5 ′ ppp) of double-stranded RNA (dsRNA) and short dsRNA (Goubau et al, 2014; Hornung et al, 2006; Luo et al, 2011; Schlee et al, 2009).”
The intrinsically disordered CARDs‐Helicase linker in RIG‐I is a molecular gate for RNA proofreading
Schweibenz, B., Devarkar, S. C., Solotchi, M., Craig, C., Zheng, J., Pascal, B. D., Gokhale, S., Xie, P., Griffin, P. R., & Patel, S. S. (2022) · The EMBO Journal · doi:10.15252/embj.2021109782 · Cited by 18
“RIG-I recognizes short blunt-ended double-stranded (ds) RNAs with 5’-triphosphate (5’ppp), 5’-diphosphate (5’pp), and 5’-m7G cap as PAMPs (pathogen-associated molecular pattern) (Jiang et al , 2011; Goubau et al , 2014; Schuberth-Wagner et al , 2015; Devarkar et al , 2016).”
An RNA Molecule Derived From Sendai Virus DI Particles Induces Antitumor Immunity and Cancer Cell-selective Apoptosis
Liu, L., Nishikawa, T., & Kaneda, Y. (2015) · Molecular Therapy · doi:10.1038/mt.2015.201 · Cited by 18
SAMD9 senses cytosolic double-stranded nucleic acids in epithelial and mesenchymal cells to induce antiviral immunity
Hou, G., Beatty, W. L., Ren, L., Ooi, Y. S., Son, J., Zhu, Y., Sheng, Q., Huang, W., Li, D., Liu, C., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59090-w · Cited by 16
“RIG-I preferentially binds to uncapped RNA bearing a triphosphate group 7 or a diphosphate group 8 , while MDA5 recognizes long dsRNA 9 .”
Influential
Human C1q Regulates Influenza A Virus Infection and Inflammatory Response via Its Globular Domain
Varghese, P. M., Kishore, U., & Rajkumari, R. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23063045 · Cited by 18
“For example, TLR3 is known to recognise dsRNA in endosomes and unfamiliar RNA structures that are present in phagocytosed cells infected with IAVs [29,30].”
BackgroundInfluential
Crosstalk between Autophagy and RLR Signaling
Ke, P. (2023) · Cells · doi:10.3390/cells12060956 · Cited by 17
The molecular language of RNA 5′ ends: guardians of RNA identity and immunity
Avila‐Bonilla, R. G., & Macías, S. (2024) · RNA · doi:10.1261/rna.079942.124 · Cited by 17
“Uncapped dsRNAs typically accumulate during the replication of ssRNA (+) or ( − ) strand viruses (Hornung et al. 2006; Pichlmair et al. 2006; Rehwinkel et al. 2010; Wang et al. 2010; Goubau et al. 2014; Ren et al. 2019).”
Background
Crosstalk between vault RNAs and innate immunity
Avila‐Bonilla, R. G., & Martínez-Montero, J. P. (2024) · Molecular Biology Reports · doi:10.1007/s11033-024-09305-y · Cited by 17
“These transcription factors cooperate to initiate the expression of type I IFN and proinflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), and IL-8 [12, 20–23].”
Background
Synthetic Agonists of Nod-Like, Rig-I-Like, and C-Type Lectin Receptors for Probing the Inflammatory Immune Response
Nielsen, A. E., Hantho, J. D., & Mancini, R. J. (2017) · Future Medicinal Chemistry · doi:10.4155/fmc-2017-0101 · Cited by 17
Early innate immune response triggered by the human respiratory syncytial virus and its regulation by ubiquitination/deubiquitination processes
Martin‐Vicente, M., Resino, S., & Martínez, I. (2022) · Journal of Biomedical Science · doi:10.1186/s12929-022-00793-3 · Cited by 18
Genetic determinants of host immunity against human rhinovirus infections
Lamborn, I. T., & Su, H. C. (2020) · Human Genetics · doi:10.1007/s00439-020-02137-3 · Cited by 17
Immunogenicity Risk Assessment for Nucleic Acid Therapeutics: A Comprehensive Evaluation for ASO, siRNA, and Nonvaccine mRNA/LNP Therapies by the IQ Consortium
Grudzinska‐Goebel, J., Braun, M., Chen, L., Gupta, S., Lohmann, S., Morais, P., Niu, T., Tarcsa, E., Tourdot, S., Youssef, A. S., et al. (2025) · Nucleic Acid Therapeutics · doi:10.1177/21593337251387423 · Cited by 17
Zebrafish prmt2 Attenuates Antiviral Innate Immunity by Targeting traf6
Zhu, J., Li, X., Sun, X., Zhou, Z., Cai, X., Liu, X., Wang, J., & Xiao, W. (2021) · The Journal of Immunology · doi:10.4049/jimmunol.2100627 · Cited by 15
Early Events in Reovirus Infection Influence Induction of Innate Immune Response
Abad, A. T., & Danthi, P. (2022) · Journal of Virology · doi:10.1128/jvi.00917-22 · Cited by 15
“71 Reovirus infection triggers an innate immune response mediated by retinoic acid-inducible 72 gene-I (RIG-I) and melanoma-differentiation associated 5 (MDA5), which are members of the 73 RIG-I like receptor (RLR) family of proteins(16-20).”
BackgroundInfluential
Mayaro virus infection elicits a robust pro-inflammatory and antiviral response in human macrophages
Hernández-Sarmiento, L. J., Tamayo-Molina, Y. S., Valdés‐López, J. F., & Inchima, S. U. (2024) · Acta Tropica · doi:10.1016/j.actatropica.2024.107146 · Cited by 14
Effective synthesis of circRNA via a thermostable T7 RNA polymerase variant as the catalyst
He, W., Zhang, X., Zou, Y., Li, J., Chang, L., He, Y.-C., Jin, Q., & Ye, J. (2024) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2024.1356354 · Cited by 16
“…which may result in a strong immune response against RNA drugs, has been detected by researchers (Kato et al., 2006; Pichlmair et al., 2006; Goubau et al., 2014). dsRNA byproducts were produced at a proportion of 1.98 ± 0.04 ×10 – 4 of the total yield of RNA products catalyzed by T7 RNAP…”
BackgroundInfluential
Mismatches in the Influenza A Virus RNA Panhandle Prevent Retinoic Acid-Inducible Gene I (RIG-I) Sensing by Impairing RNA/RIG-I Complex Formation
Anchisi, S., Guerra, J., Mottet-Osman, G., & Garcin, D. (2015) · Journal of Virology · doi:10.1128/jvi.01671-15 · Cited by 15
Nucleic Acid-Induced Signaling in Chronic Viral Liver Disease
Suarez, A. A. R., Testoni, B., Baumert, T. F., & Lupberger, J. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.624034 · Cited by 18
Harnessing the Activation of RIG-I Like Receptors to Inhibit Glioblastoma Tumorigenesis
Bufalieri, F., Basili, I., Marcotullio, L. D., & Infante, P. (2021) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2021.710171 · Cited by 14
“…double-strand RNAs (dsRNAs), single-strand RNAs (ssRNAs) forming secondary structure (i.e., hairpin or panhandle conformations), and RNAs with uncapped diphosphate (PP) groups at the 5′ (Hornung et al., 2006; Pichlmair et al., 2006; Schmidt et al., 2009; Schlee, 2013; Goubau et al., 2014).”
Background
Hepatitis C virus replicative double-stranded RNA is a potent interferon inducer that triggers interferon production through MDA5
Du, X., Pan, T., Xu, J. C., Zhang, Y., Song, W., Yi, Z., & Yuan, Z. (2016) · Journal of General Virology · doi:10.1099/jgv.0.000607 · Cited by 15
A conserved isoleucine in the binding pocket of RIG-I controls immune tolerance to mitochondrial RNA
de Regt, A. K., Anand, K., Ciupka, K., Bender, F., Gatterdam, K., Putschli, B., Fußhöller, D. M., Hilbig, D., Kirchhoff, A., Hunkler, C., et al. (2023) · Nucleic Acids Research · doi:10.1093/nar/gkad835 · Cited by 14
Grass carp (Ctenopharyngodon idella) SIRT3 enhances MAVS-mediated antiviral innate immunity in response to GCRV infection
Zhu, C., Liu, W., Jia, S., Sun, X., Wang, Z., Deng, H., Bai, Y., Xiao, W., & Liu, X. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.740871 · Cited by 13
m6A Methylation in Regulation of Antiviral Innate Immunity
Karandashov, I., Kostyusheva, A., Kachanov, A., Dukich, M., Ponomareva, N., Brezgin, S., Lukashev, A., Pokrovsky, V. S., Chulanov, V., & Kostyushev, D. S. (2024) · Viruses · doi:10.3390/v16040601 · Cited by 15
“RIG-I recognizes relatively short ssRNA and dsRNA (up to 1 kb) with triphosphate or diphosphate fragments at the 5 ′ -end [70].”
Background
Innate Sensing of Viral Nucleic Acids and Their Use in Antiviral Vaccine Development
Enya, T., & Ross, S. R. (2025) · Vaccines · doi:10.3390/vaccines13020193 · Cited by 15
“In contrast, MDA5 detects long dsRNA generated during RNA virus replication, as well as synthetic RNAs, including poly I:C; the recognition of dsRNA by MDA5 activates IRF3 and NF κ B, also leading to increased production of IFN-I [109,110] (Figure 2).”
Molecular cloning and functional characterization of feline MAVS
Wu, H., Zhang, X., Liu, C., Liu, D., Liu, J., Wang, G., Tian, J., & Qu, L. (2015) · Immunologic Research · doi:10.1007/s12026-015-8682-9 · Cited by 15
Innate sensing of mRNA vaccines
Wuebben, C., Bartok, E., & Hartmann, G. (2022) · Current Opinion in Immunology · doi:10.1016/j.coi.2022.102249 · Cited by 16
How Many Mammalian Reovirus Proteins are involved in the Control of the Interferon Response?
Lanoie, D., Boudreault, S., Bisaillon, M., & Lemay, G. (2019) · Pathogens · doi:10.3390/pathogens8020083 · Cited by 14
“(PAMP) recognized by RIG-I [13]; however, again, it is not clear if these ends are actually exposed in the”
BackgroundInfluential
The Reovirus σ3 Protein Inhibits NF-κB-Dependent Antiviral Signaling
McNamara, A. J., Brooks, A. D., & Danthi, P. (2022) · Journal of Virology · doi:10.1128/jvi.00515-22 · Cited by 13
Orange-spotted grouper nervous necrosis virus-encoded protein A induces interferon expression via RIG-I/MDA5-MAVS-TBK1-IRF3 signaling in fish cells
Huang, S., Huang, Y., Su, T., Huang, R., Su, L., Wu, Y., Weng, S., He, J., & Xie, J. (2023) · Microbiology Spectrum · doi:10.1128/spectrum.04532-22 · Cited by 13
“Lots of research on RIG-I agonists indicated that RIG-I plays a key role in the recognition of RNA viruses including Sendai virus (SeV) (39, 40), reovirus (41), vesicular stomatitis virus (42), Newcastle disease virus (43), and influenza virus (44).”
Background
Host Immune Response to Dengue Virus Infection: Friend or Foe?
Dhole, P., Zaidi, A., Nariya, H. K., Sinha, S., Jinesh, S., & Srivastava, S. (2024) · Immuno · doi:10.3390/immuno4040033 · Cited by 15
“…and prevents mitochondrial DNA sensing [135,136] These cells possess pattern recognition receptors (PRRs) that detect pathogen-associated molecular patterns (PAMPs) that include double-stranded or single-stranded RNA and diphosphate structures generated during virus replication [140–143].”
IKKε isoform switching governs the immune response against EV71 infection
Chang, Y., Liao, Y., Chen, M., Chang, S., Huang, Y., Ho, B., & Yu, S. (2021) · Communications Biology · doi:10.1038/s42003-021-02187-x · Cited by 13
Mimicking Pathogens to Augment the Potency of Liposomal Cancer Vaccines
Twilhaar, M. K. N., Czentner, L., van Nostrum, C. F., Storm, G., & den Haan, J. M. M. (2021) · Pharmaceutics · doi:10.3390/pharmaceutics13070954 · Cited by 13
The Role of RNA Editing in the Immune Response
Ahmad, S., Mu, X. N., & Hur, S. (2020) · Methods in molecular biology · doi:10.1007/978-1-0716-0787-9_17 · Cited by 12
A Simplified Method to Produce Mrnas and Functional Proteins From Synthetic Double-Stranded DNA Templates
Tossberg, J. T., Esmond, T., & Aune, T. M. (2020) · BioTechniques · doi:10.2144/btn-2020-0037 · Cited by 13
Proofreading mechanisms of the innate immune receptor RIG-I: distinguishing self and viral RNA
Solotchi, M., & Patel, S. S. (2024) · Biochemical Society Transactions · doi:10.1042/bst20230724 · Cited by 12
Role of the Innate Immune Response in Glomerular Disease Pathogenesis: Focus on Podocytes
Issa, W., Njeim, R., Carrazco, A., Burke, G. W., & Mitrofanova, A. V. (2024) · Cells · doi:10.3390/cells13131157 · Cited by 13
“In addition to the 5 ′ -triphosphate structure, the 5 ′ -diphosphate moiety can also be recognized by RIG-I [96].”
Background
Endosomes serve as signaling platforms for RIG-I ubiquitination and activation
Chen, K., Yang, C.-Y., Shu, S.-G., Lo, Y.-C., Lee, K.-W., Wang, L.-C., Chen, J.-B., Shih, M.-C., Chang, H.-C., Hsiao, Y.-J., et al. (2024) · Science Advances · doi:10.1126/sciadv.adq0660 · Cited by 12
“Notably, RIG-I preferentially recognizes 5 ′ - triphosphate (PPP) or 5 ′ - diphosphate–containing double-stranded RNAs, while MDA5 binds to long double-stranded RNA (dsRNA) lacking 2 ′ - O-methylation at the 5 ′ cap ( 7 – 9 ).”
Identification of a second binding site on the TRIM25 B30.2 domain
D’Cruz, A. A., Kershaw, N. J., Hayman, T. J., Linossi, E. M., Chiang, J. J., Wang, M. K., Dagley, L. F., Kolesnik, T. B., Zhang, J., Masters, S. L., et al. (2017) · Biochemical Journal · doi:10.1042/bcj20170427 · Cited by 12
Loss of IKK Subunits Limits NF-κB Signaling in Reovirus-Infected Cells
McNamara, A. J., & Danthi, P. (2020) · Journal of Virology · doi:10.1128/jvi.00382-20 · Cited by 12
Epigenetic regulation of RNA sensors: Sentinels of immune response
Khan, M. I., Nur, S. M., Adhami, V. M., & Mukhtar, H. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2020.12.028 · Cited by 12
Zebrafish sirt5 Negatively Regulates Antiviral Innate Immunity by Attenuating Phosphorylation and Ubiquitination of mavs
Chen, X., Fan, S., Zhu, C., Liao, Q., Tang, J., Yu, G., Cai, X., Ouyang, G., Xiao, W., & Liu, X. (2022) · The Journal of Immunology · doi:10.4049/jimmunol.2100983 · Cited by 13
A rational roadmap for SARS-CoV-2/COVID-19 pharmacotherapeutic research and developmentPreprint
Alexander, S., Armstrong, J. F., Davenport, A. P., Davies, J. A., Faccenda, E., Harding, S. D., Levi‐Schaffer, F., Pawson, A. J., Southan, C., & Spedding, M. (2020) · doi:10.22541/au.158679935.58510327 · Cited by 12
Research progress of mRNA vaccines for infectious diseases
Zhang, Z., Du, J., Zhang, D., Han, R., Wu, X., & Liang, Y. (2025) · European journal of medical research · doi:10.1186/s40001-025-03060-x · Cited by 19
Unlocking mRNA-driven CRISPR-Cas9 gene therapy via optimizing mRNA and the delivery vectors
Wang, S., Xu, X., Viitala, T., Shu, Y., & Zhang, H. (2025) · Molecular Therapy — Nucleic Acids · doi:10.1016/j.omtn.2025.102737 · Cited by 14
Duox2 is required for the transcription of pattern recognition receptors in acute viral lung infection: An interferon-independent regulatory mechanism
Hong, S., Kim, J. Y., Kim, H., Kim, D., Won, T., Han, D. H., Rhee, C., & Kim, H. J. (2016) · Antiviral Research · doi:10.1016/j.antiviral.2016.08.017 · Cited by 11
The intersection molecule MDA5 in Cancer and COVID-19
Jin, R., Cao, X., Lu, M., Gao, Q. S., & Ma, T. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.963051 · Cited by 11
Initial activation of STAT2 induced by IAV infection is critical for innate antiviral immunity
Li, X., Liu, S., Rai, K. R., Zhou, W., Wang, S., Chi, X., Guo, G., Chen, J., & Liu, S. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.960544 · Cited by 12
Effective Synthesis of High-Integrity mRNA Using In Vitro Transcription
He, W., Zhang, X., Zou, Y., Li, J., Wang, C., He, Y.-C., Jin, Q., & Ye, J. (2024) · Molecules · doi:10.3390/molecules29112461 · Cited by 13
“Nevertheless, the activation of pattern recognition receptors (RIG-I, MDA5 and so on) by dsRNA has adverse consequences, including the inhibition of protein synthesis and cell death, which can impact the efficacy of mRNA therapy [23–25].”
Background
Viral RNA capping: Mechanisms and antiviral therapy
Chen, S., Jiang, Z., Li, Q., Pan, W., Chen, Y., & Liu, J. (2024) · Journal of Medical Virology · doi:10.1002/jmv.29622 · Cited by 10
“I, struggles to recognize Cap 1, 92 aligning with the viral mRNA's Cap 1 structure evading the immunosuppressive effects of IFITs.”
Background
Energetics of Preferential Binding of Retinoic Acid-Inducible Gene-I to Double-Stranded Viral RNAs with 5′ Tri-/Diphosphate over 5′ Monophosphate
Kumar, A., & Satpati, P. (2018) · ACS Omega · doi:10.1021/acsomega.7b02019 · Cited by 10
Innate Immune Stimulation in Cancer Therapy
Duewell, P., Heidegger, S. M., & Kobold, S. (2019) · Hematology/Oncology Clinics of North America · doi:10.1016/j.hoc.2018.12.002 · Cited by 10
Induction of Robust Type I Interferon Levels by Oncolytic Reovirus Requires Both Viral Replication and Interferon-α/β Receptor Signaling
Oosenbrug, T., van den Wollenberg, D. J. M., Duits, E. W., Hoeben, R. C., & Ressing, M. E. (2021) · Human Gene Therapy · doi:10.1089/hum.2021.140 · Cited by 10
Re-Examining Rotavirus Innate Immune Evasion: Potential Applications of the Reverse Genetics System
Antia, A., Pinski, A. N., & Ding, S. (2022) · mBio · doi:10.1128/mbio.01308-22 · Cited by 10
Sensing infection and tissue damage
Sousa, C. R. E. (2017) · EMBO Molecular Medicine · doi:10.15252/emmm.201607227 · Cited by 11
Genetic variants in RIG-I-like receptor influences HCV clearance in Chinese Han population
Wu, X., Zang, F., Liu, M., Zhuo, L., Wu, J., Xia, X., Feng, Y., Yu, R., Huang, P., & Yang, S. (2019) · Epidemiology and Infection · doi:10.1017/s0950268819000827 · Cited by 10
“Environment, viral and host factors have been proved to be the influential factor in HCV spontaneous clearance and treatment response [4].”
Background
Signal‐transducing innate receptors in tumor immunity
Hangai, S., Kimura, Y., Taniguchi, T., & Yanai, H. (2021) · Cancer Science · doi:10.1111/cas.14848 · Cited by 12
Grass carp PRMT6 negatively regulates innate immunity by inhibiting the TBK1/IRF3 binding and cutting down IRF3 phosphorylation level
Jiang, Z., Cheng, X., Sun, Z., Hu, J., Xu, X., Li, M., Feng, Z., & Hu, C. (2022) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2022.104351 · Cited by 10
PLAAT1 inhibits type I interferon response via degradation of IRF3 and IRF7 in Zebrafish
Zhao, X., Huang, W., Shi, Y., Guo, J., Xiao, H., Ji, N., Feng, J., Dang, H., & Zou, J. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.979919 · Cited by 10
RIGulation of STING expression: at the crossroads of viral RNA and DNA sensing pathways
Liu, Y., Lin, R., & Olagnier, D. P. (2017) · Inflammation and Cell Signaling · doi:10.14800/ics.1491 · Cited by 10
“Among which, RIG-I specifically recognizes short dsRNA bearing a 5′ end diphosphate or triphosphate group (5′pp or 5′ppp) [18, 19].”
Background
Induction of apoptosis by double-stranded RNA was present in the last common ancestor of cnidarian and bilaterian animals
Kozlovski, I., Jaimes‐Becerra, A., Sharoni, T., Lewandowska, M., Karmi, O., & Moran, Y. (2024) · PLoS Pathogens · doi:10.1371/journal.ppat.1012320 · Cited by 9
“…vertebrates, poly(I: C), which mimics dsRNA, binds to and triggers the activation of the RNA sensors PKR, OAS1, TLR3, MDA5 and RIG-I, and consequently poly(I:C) or its derivatives have been used as a tool to identify and characterize dsRNA recognition receptors and ligand requirements [38,99– 103].”
Method
5′ terminal nucleotide determines the immunogenicity of IVT RNAs
Wołczyk, M., Szymański, J., Trus, I., Naz, Z., Tame, T., Bolembach, A. A., Choudhury, N. R., Kasztelan, K., Rappsilber, J., Dziembowski, A., et al. (2024) · Nucleic Acids Research · doi:10.1093/nar/gkae1252 · Cited by 9
“The most potent activators of RIG-I are short, blunt, double-stranded RNAs (dsRNAs) capped with 5 (cid:2) -ppp or 5 (cid:2) - pp moieties ( 8–11 ).”
RNA innate immunity constitutes a barrier for interspecies chimerism
Hu, Y., Sun, H., Sakurai, M., Luo, Z., Jones, A. E., Cheng, T., Huang, J., Liu, L., Zheng, C., Li, J., et al. (2025) · Cell · doi:10.1016/j.cell.2025.10.039 · Cited by 16
N6-methyladenosine modification of viral RNA and its role during the recognition process of RIG-I-like receptors
Li, H., Guo, Y., Qi, W., & Liao, M. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.1031200 · Cited by 12
Advances in transposable elements: from mechanisms to applications in mammalian genomics
Han, M., Perkins, M. H., Novaes, L. S., Xu, T., & Chang, H. (2023) · Frontiers in Genetics · doi:10.3389/fgene.2023.1290146 · Cited by 9
Transcriptome Analysis of Human Dermal Cells Infected with Candida auris Identified Unique Pathogenesis/Defensive Mechanisms Particularly Ferroptosis
Fayed, B. E., Shakartalla, S. B., Sabbah, H., Dalle, H., Tannira, M., Senok, A. C., & Soliman, S. S. M. (2024) · Mycopathologia · doi:10.1007/s11046-024-00868-9 · Cited by 9
“RIG-I-like receptor is one of the pathogen-specific pattern recognition receptors that can recognize the pathogen-specific 5 ′ -di or -triphospate RNA [93].”
Combined roles of ATP and small hairpin RNA in the activation of RIG-I revealed by solution-based analysis
Shah, N. K., Beckham, S. A., Wilce, J. A., & Wilce, M. C. J. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx1307 · Cited by 9
“RIG-I senses dsRNA with a 5′ppp or 5′pp with high affinity (2,35), but shows only weak affinity for dsRNA with a 5′p (35).”
Background
Systematic editing of synthetic RIG-I ligands to produce effective antiviral and anti-tumor RNA immunotherapies
Lee, J. H., Park, E.-B., Min, J., Sung, S.-E., Jang, Y., Shin, J. S., Chun, D., Kim, K., Hwang, J., Lee, M., et al. (2018) · Nucleic Acids Research · doi:10.1093/nar/gky039 · Cited by 9
“RIG-I recognizes dsRNAs containing uncapped 5′-PPP (11) or 5′-PP (12) which are found in RNA virus genomes and therefore produced during viral replication.”
Background
Retracted
Identification and characterization of an atypical RIG-I encoded by planarian Dugesia japonica and its essential role in the immune response
Li, N., Li, A., ZHENG, K. C., Liu, X., Gao, L., Liu, D., Deng, H., Wu, W., Liu, B., Zhao, B., et al. (2018) · Developmental & Comparative Immunology · doi:10.1016/j.dci.2018.10.007 · Cited by 9
Structure‐guided design of immunomodulatory RNA s specifically targeting the cytoplasmic viral RNA sensor RIG ‐I
Yong, H. Y., Zheng, J., Ho, V. C. Y., Nguyen, M. T., Fink, K., Griffin, P. R., & Luo, D. (2019) · FEBS Letters · doi:10.1002/1873-3468.13564 · Cited by 9
Innate immune sensors for detecting nucleic acids during infection
Ghoreshi, Z., Nakhaee, M., Samie, M., Zak, M. S., & Arefinia, N. (2022) · Journal of Laboratory Medicine · doi:10.1515/labmed-2021-0173 · Cited by 8
“RIG-I is also triggered by the 5ʹ end of triphosphorylation or 5ʹ diphosphorylated short dsRNAs [15, 16].”
Background
Induction of Interferon-Stimulated Genes Correlates with Reduced Growth of Influenza A Virus in Lungs after RIG-I Agonist Treatment of Ferrets
Schwab, L. S. U., Londrigan, S. L., Brööks, A. G., Hurt, A. C., Sahu, A., Deng, Y., Moselen, J. M., Coch, C., Zillinger, T., Hartmann, G., et al. (2022) · Journal of Virology · doi:10.1128/jvi.00559-22 · Cited by 8
Zebrafish mavs Is Essential for Antiviral Innate Immunity
Ouyang, G., Liao, Q., Fan, S., Cai, X., Wang, J., Liu, X., & Xiao, W. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2200126 · Cited by 8
mRNA vaccines against infectious diseases and future direction
Aleem, M. T., Munir, F., Shakoor, A., & Gao, F. (2024) · International Immunopharmacology · doi:10.1016/j.intimp.2024.112320 · Cited by 10
Porcine epidemic diarrhea virus nsp14 inhibited IFN-Ⅰ production by targeting RIG-I for degradation
Li, S., Wang, L., Wen, Y., Han, J., Hou, J., Hou, Z., Xie, J., Li, H., Li, X., Yang, Y., et al. (2025) · Virology · doi:10.1016/j.virol.2025.110451 · Cited by 8
RNF19a inhibits antiviral immune response to RNA viruses through degradation of TBK1
Yang, Y., Cao, X., Huang, L., & Yang, A. (2022) · Molecular Immunology · doi:10.1016/j.molimm.2021.12.021 · Cited by 8
Nucleic Acid Sensing Pathways in DNA Repair Targeted Cancer Therapy
Xie, B., & Luo, A. (2022) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2022.903781 · Cited by 9
“…until now, chemotherapy and radiotherapy have remained the important treatment options for a variety of cancers (Hellmann et al., 2016; Chu et al., 2018; Qin et al., 2018; De Ruysscher et al., 2019; Grassberger et al., 2019; Galluzzi et al., 2020; Huang and Zhou, 2020; McLaughlin et al., 2020).”
Background

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: Schlee, Martin
Pruijssers, Andrea J.
Zillinger, Thomas
Goldeck, Marion
Fujimura, Tsutomu
Rehwinkel, Jan
Barchet, Winfried
Dermody, Terence S.
Hartmann, Gunther
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2014-08-10
Volume: 514
Issue: 7522
Pages: 372-375
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature13590
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: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
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

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

Antiviral immunity via RIG-I-mediated recognition of RNA bearing 5'-diphosphates

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks