Innate immune restriction and antagonism of viral RNA lacking 2׳-O methylation
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N-7 and 2'-O methylation of host cell mRNA occurs in the nucleus and results in the generation of cap structures (cap 0, m(7)GpppN; cap 1, m(7)GpppNm) that control gene expression by modulating nuclear export, splicing, turnover, and protein synthesis. Remarkably, RNA cap modification also contributes to mammalian cell host defense as viral RNA lacking 2'-O methylation is sensed and inhibited by IFIT1, an interferon (IFN) stimulated gene (ISG). Accordingly, pathogenic viruses that replicate in the cytoplasm have evolved mechanisms to circumvent IFIT1 restriction and facilitate infection of mammalian cells. These include: (a) generating cap 1 structures on their RNA through cap-snatching or virally-encoded 2'-O methyltransferases, (b) using cap-independent means of translation, or (c) using RNA secondary structural motifs to antagonize IFIT1 binding. This review will discuss new insights as to how specific modifications at the 5'-end of viral RNA modulate host pathogen recognition responses to promote infection and disease.
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The cap1 structure can be used as a signature of self-RNA, thus reducing activation of pattern recognition receptor (PRR) and improving translation efficiency of mRNA in vivo.
“Since the cap1 structure has only been described to date in eukaryotic mRNAs, it can be used as a signature of self-RNA, thus reducing the activation of pattern recognition receptor (PRR) and consequently improving translation efficiency of mRNA in vivo.119”
From Advances in COVID-19 mRNA vaccine development (2022) · cites this paper as [119]
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Advances in COVID-19 mRNA vaccine development
Fang, E., Liu, X., Li, M., Zhang, Z., Song, L., Zhu, B., Wu, X., Liu, J., Zhao, D., & Li, Y. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-00950-y · Cited by 601 · see citing works
Hartmann, G. (2017) · Advances in Immunology · doi:10.1016/bs.ai.2016.11.001 · Cited by 285 · 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
- Authors
- Hyde, J. L., & Diamond, M. S.
- Affiliations
- Washington University in St. Louis (US)
- Corresponding author
- Diamond, Michael S.
- Venue
- Virology
- Publisher
- Elsevier BV
- Published
- 2015-05
- Volume
- 479-480
- Pages
- 66-74
- ISSN
- 0042-6822 (ISSN-L)
- PMC
- PMC4424151
- OpenAlex
- W2038167124
- Cited by
- 194
- References
- 113
- Citations by year
- 2026: 10 · 2025: 13 · 2024: 21 · 2023: 22 · 2022: 27 · 2021: 22 · 2020: 29 · 2019: 14 · 2018: 11 · 2017: 10 · 2016: 12 · 2015: 3
- FWCI
- 1.13
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Virology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NIH (U19 AI083019, U19 AI106772, R01 AI104972, R01 AI104002)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › interferon and immune responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA modifications and cancer
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- innate immunity, viral RNA, 2'-O-methylation, IFIT1, interferon-stimulated genes, cap-snatching, 2'-O-methyltransferase, cap-independent translation, RNA secondary structure, viral RNA sensing, host defense
- MeSH terms
- Carrier Proteins, Nucleic Acid Conformation, RNA Caps, RNA, Messenger, RNA, Viral, Viruses, RNA-Binding Proteins, RNA Stability, Adaptor Proteins, Signal Transducing, Host-Pathogen Interactions, Immune Evasion
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 ›
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