A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation

Antonio Gregorio Dias Junior¹, Natalia G Sampaio², Jan Rehwinkel³

Affiliations

¹ Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK. Electronic address: https://twitter.com/GregorioDias1.
² Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
³ Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK. Electronic address: jan.rehwinkel@imm.ox.ac.uk.

PMID: 30201512
PMCID: PMC6319154
DOI: 10.1016/j.tim.2018.08.007

Free PMC article

Review

A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation

Antonio Gregorio Dias Junior et al. Trends Microbiol. 2019 Jan.

Free PMC article

. 2019 Jan;27(1):75-85.

doi: 10.1016/j.tim.2018.08.007. Epub 2018 Sep 7.

Authors

Antonio Gregorio Dias Junior¹, Natalia G Sampaio², Jan Rehwinkel³

Affiliations

¹ Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK. Electronic address: https://twitter.com/GregorioDias1.
² Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK.
³ Medical Research Council Human Immunology Unit, Medical Research Council Weatherall Institute of Molecular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 9DS, UK. Electronic address: jan.rehwinkel@imm.ox.ac.uk.

PMID: 30201512
PMCID: PMC6319154
DOI: 10.1016/j.tim.2018.08.007

Abstract

Induction of interferons during viral infection is mediated by cellular proteins that recognise viral nucleic acids. MDA5 is one such sensor of virus presence and is activated by RNA. MDA5 is required for immunity against several classes of viruses, including picornaviruses. Recent work showed that mutations in the IFIH1 gene, encoding MDA5, lead to interferon-driven autoinflammatory diseases. Together with observations made in cancer cells, this suggests that MDA5 detects cellular RNAs in addition to viral RNAs. It is therefore important to understand the properties of the RNAs which activate MDA5. New data indicate that RNA length and secondary structure are features sensed by MDA5. We review these developments and discuss how MDA5 strikes a balance between antiviral immunity and autoinflammation.

Keywords: IFIH1; MDA5; RNA; antiviral defence; autoinflammation; type I interferon.

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References

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A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation

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A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation

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