RIG-I detects viral genomic RNA during negative-strand RNA virus infection
Open accessAbstract
RIG-I is a key mediator of antiviral immunity, able to couple detection of infection by RNA viruses to the induction of interferons. Natural RIG-I stimulatory RNAs have variously been proposed to correspond to virus genomes, virus replication intermediates, viral transcripts, or self-RNA cleaved by RNase L. However, the relative contribution of each of these RNA species to RIG-I activation and interferon induction in virus-infected cells is not known. Here, we use three approaches to identify physiological RIG-I agonists in cells infected with influenza A virus or Sendai virus. We show that RIG-I agonists are exclusively generated by the process of virus replication and correspond to full-length virus genomes. Therefore, nongenomic viral transcripts, short replication intermediates, and cleaved self-RNA do not contribute substantially to interferon induction in cells infected with these negative strand RNA viruses. Rather, single-stranded RNA viral genomes bearing 5'-triphosphates constitute the natural RIG-I agonists that trigger cell-intrinsic innate immune responses during infection.
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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 [13]
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Maelfait, J., Liverpool, L., Bridgeman, A., Ragan, K. B., Upton, J. W., & Rehwinkel, J. (2017) · The EMBO Journal · doi:10.15252/embj.201796476 · Cited by 237 · see citing works
Self-citationCRISPR RNAs Trigger Innate Immune Responses in Human Cells
Kim, S., Koo, T., Jee, H.-G., Cho, H.-Y., Lee, G., Lim, D.-G., Shin, H. S., & Kim, J.-S. (2018) · Genome Research · doi:10.1101/gr.231936.117 · Cited by 222 · see citing works
Multi-layered stochasticity and paracrine signal propagation shape the type-I interferon response
Rand, U., Rinas, M., Schwerk, J., Nöhren, G., Linnes, M., Kröger, A., Flossdorf, M., Kály‐Kullai, K., Hauser, H., Höfer, T., et al. (2012) · Molecular Systems Biology · doi:10.1038/msb.2012.17 · Cited by 147 · see citing works
Immune responses to influenza virus and its correlation to age and inherited factors
Bahadoran, A., Lee, S. H., Wang, S. M., Manikam, R., Rajarajeswaran, J., Raju, C. S., & Sekaran, S. D. (2016) · Frontiers in Microbiology · doi:10.3389/fmicb.2016.01841 · Cited by 79 · see citing works
- Authors
- Rehwinkel, J., Tan, C. P., Goubau, D., Schulz, O., Pichlmair, A., Bier, K., Robb, N., Vreede, F., Barclay, W., Fodor, E., & Reis e Sousa, C.
- Affiliations
- Cancer Research UK (GB)
- University of Oxford (GB)
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-02
- Volume
- 140
- Issue
- 3
- Pages
- 397-408
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2014960200
- Cited by
- 585
- References
- 88
- Citations by year
- 2026: 17 · 2025: 33 · 2024: 30 · 2023: 27 · 2022: 23 · 2021: 43 · 2020: 31 · 2019: 30 · 2018: 33 · 2017: 20 · 2016: 36 · 2015: 32 · 2014: 44 · 2013: 54 · 2012: 46
- FWCI
- 25.52
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1262 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cancer Research UK
- Fondation Bettencourt Schueller
- Medical Research Council
- Biotechnology and Biological Sciences Research Council
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- RIG-I, negative-strand RNA viruses, viral RNA genome, interferon induction, antiviral innate immunity, influenza A virus, Sendai virus, 5'-triphosphate RNA, RNA virus replication, RIG-I agonist
- MeSH terms
- DEAD Box Protein 58, Roundabout Proteins, Animals, Cell Line, Dogs, Humans, Interferons, Membrane Proteins, Nerve Tissue Proteins, Receptors, Cell Surface, Receptors, Immunologic, RNA Virus Infections, RNA Viruses, RNA, Viral, Virus Replication, Mice, DEAD-box RNA Helicases
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