Chicken MDA5 Senses Short Double-Stranded RNA with Implications for Antiviral Response against Avian Influenza Viruses in Chicken
Chicken MDA5 Senses Short Double-Stranded RNA with Implications for Antiviral Response against Avian Influenza Viruses in Chicken
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DOI：
10.1159/000351583
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发表时间：
2014-01-01
影响因子：
5.3
通讯作者：
Saito, Takehiko
中科院分区：
文献类型：
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作者：
Hayashi, Tsuyoshi;Watanabe, Chiaki;Saito, Takehiko
哺乳动物黑色素瘤分化相关基因5（MDA 5）和视黄酸诱导基因I（RIG-I）根据长度选择性地有义双链RNA（dsRNA），以及各种RNA病毒以诱导抗病毒应答。RIG-I在诱导针对流感病毒感染的抗病毒应答中起主要作用，但被认为在鸡中缺乏，这使得鸡MDA 5（chMDA 5）的功能受到关注。在这里，我们表明，chMDA 5，不像哺乳动物MDA 5，优先感测较短的dsRNA合成类似物，聚（I：C），在鸡DF-1成纤维细胞。证明了半胱天冬酶激活和募集结构域对于chMDA 5介导的鸡干扰素β（chIFNI 3）诱导及其与线粒体抗病毒信号蛋白的相互作用的需要。我们还发现chMDA 5参与了chIFNI 3诱导抗禽流感病毒感染。我们的研究结果表明，chMDA 5部分补偿RIG-升降机鸡的功能，并强调了chMDA 5在鸡先天免疫反应中的重要性。(C)2013 S. Karger AG，巴塞尔
Mammalian melanoma differentiation-associated gene-5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense double-stranded RNA (dsRNA) according to length, as well as various RNA viruses to induce an antiviral response. RIG-I, which plays a predominant role in the induction of antiviral responses against influenza virus infection, has been considered to be lacking in chicken, putting the function of chicken MDA5 (chMDA5) under the spotlight. Here, we show that chMDA5, unlike mammalian MDA5, preferentially senses shorter dsRNA synthetic analogues, poly(I:C), in chicken DF-1 fibroblasts. A requirement for caspase activation and recruitment domains for chMDA5-mediated chicken interferon beta (chIFNI3) induction and its interaction with mitochondrial antiviral signaling proteins were demonstrated. We also found that chMDA5 is involved in chIFNI3 induction against avian influenza virus infection. Our findings imply that chMDA5 compensates in part the function of RIG-lift chicken, and highlights the importance of chMDA5 in the innate immune response in chicken. (C) 2013 S. Karger AG, Basel