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.
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.
Trends Microbiol. 2019 Jan;27(1):75-85. doi: 10.1016/j.tim.2018.08.007. Epub 2018 Sep 7.
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.
病毒感染时干扰素的诱导是由识别病毒核酸的细胞蛋白介导的。MDA5 就是这样一种病毒存在的传感器，它被 RNA 激活。MDA5 是对抗包括小核糖核酸病毒在内的几类病毒所必需的。最近的工作表明，编码 MDA5 的 IFIH1 基因突变导致干扰素驱动的自身炎症性疾病。结合在癌细胞中观察到的结果，这表明 MDA5 除了检测病毒 RNA 外，还检测细胞 RNA。因此，了解激活 MDA5 的 RNA 的特性非常重要。新的数据表明，RNA 长度和二级结构是 MDA5 感知的特征。我们回顾了这些进展，并讨论了 MDA5 如何在抗病毒免疫和自身炎症之间取得平衡。
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