Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses
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DOI：
10.1038/nature04734
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发表时间：
2006-05-04
期刊：
影响因子：
64.8
通讯作者：
Akira, S
中科院分区：
文献类型：
--
作者：
Kato, H;Takeuchi, O;Akira, S
先天免疫系统通过识别各种病毒成分(包括双链RNA)来感知病毒感染，并触发抗病毒反应(1，2)。细胞质解旋酶蛋白RIG-I(视黄酸诱导蛋白I，又称Ddx58)和MDA5(黑色素瘤分化相关基因5，又称IFIH1或HeliCard)与病毒dsRNA识别有关(3-7)。体外研究表明，RIG-I和MDA5都能检测到RNA病毒和一种合成的dsRNA类似物--多肌苷多胞酸(Poly(I：C))。虽然RIG-I在识别几种RNA病毒中的关键作用已经被阐明(8)，但MDA5的功能作用和这些dsRNA检测器在体内的关系尚未确定。在这里，我们使用MDA5缺陷小鼠(MDA5(-/-))来表明MDA5和RIG-I识别不同类型的dsRNAs：MDA5识别Poly(I：C)，RIG-I检测体外转录的dsRNAs。RNA病毒也被RIG-I和MDA5区别识别。我们发现，RIG-I对于副粘病毒、流感病毒和乙型脑炎病毒等RNA病毒的干扰素的产生是必不可少的，而MDA5对于微小核糖核酸病毒的检测是关键的。此外，与对照小鼠相比，RIG-I-/-和MDA5(-/-)小鼠对这些RNA病毒的感染高度敏感。总之，我们的数据表明，RIG-I和MDA5区分不同的RNA病毒，对宿主的抗病毒反应至关重要。
The innate immune system senses viral infection by recognizing a variety of viral components (including double-stranded (ds) RNA) and triggers antiviral responses(1,2). The cytoplasmic helicase proteins RIG-I (retinoic-acid-inducible protein I, also known as Ddx58) and MDA5 (melanoma-differentiation-associated gene 5, also known as Ifih1 or Helicard) have been implicated in viral dsRNA recognition(3-7). In vitro studies suggest that both RIG-I and MDA5 detect RNA viruses and polyinosine-polycytidylic acid (poly(I:C)), a synthetic dsRNA analogue(3). Although a critical role for RIG-I in the recognition of several RNA viruses has been clarified(8), the functional role of MDA5 and the relationship between these dsRNA detectors in vivo are yet to be determined. Here we use mice deficient in MDA5 (MDA5(-/-)) to show that MDA5 and RIG-I recognize different types of dsRNAs: MDA5 recognizes poly(I:C), and RIG-I detects in vitro transcribed dsRNAs. RNA viruses are also differentially recognized by RIG-I and MDA5. We find that RIG-I is essential for the production of interferons in response to RNA viruses including paramyxo-viruses, influenza virus and Japanese encephalitis virus, whereas MDA5 is critical for picornavirus detection. Furthermore, RIG-I-/- and MDA5(-/-) mice are highly susceptible to infection with these respective RNA viruses compared to control mice. Together, our data show that RIG-I and MDA5 distinguish different RNA viruses and are critical for host antiviral responses.