Characterization of Chicken Mda5 Activity: Regulation of IFN-β in the Absence of RIG-I Functionality
Characterization of Chicken Mda5 Activity: Regulation of IFN-β in the Absence of RIG-I Functionality
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DOI：
10.4049/jimmunol.1003712
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发表时间：
2011-05-01
影响因子：
4.4
通讯作者：
Bean, Andrew G. D.
中科院分区：
文献类型：
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作者：
Karpala, Adam J.;Stewart, Cameron;Bean, Andrew G. D.
在哺乳动物中，Mda 5和RIG-I是进化上保守的RIG样解旋酶家族的成员，在RNA病毒感染的结果中发挥关键作用。解决哺乳动物的流感感染已被证明需要RIG-I;然而，在鸡中明显缺乏RIG-I同源物引起了关于该物种如何处理流感病毒感染的有趣问题。尽管鸡能够解决某些流感病毒株，但它们对其他流感病毒株高度易感，例如高致病性禽流感H5 N1。了解鸡中的RIG样解旋酶至关重要，特别是对于开发可能使用这些系统的新疗法。考虑到这一点，我们研究了鸡中的RIG样解旋酶Mda 5。我们已经确定了鸡Mda 5同系物（ChMda 5），并评估其功能活动，涉及抗病毒反应。与哺乳动物Mda 5一样，ChMda 5表达响应于dsRNA刺激和细胞的IFN活化而上调。此外，RNA干扰介导的ChMda 5敲低表明ChMda 5在鸡细胞对dsRNA的IFN应答中起重要作用。有趣的是，虽然ChMda 5水平在流感感染期间高度上调，但ChMda 5表达的敲低似乎不会影响流感增殖。总的来说，虽然Mda 5在鸡中具有功能活性，但缺乏明显的RIG-I样功能可能导致鸡对高致病性流感的易感性。免疫学杂志，2011，186：5397-5405。
In mammals, Mda5 and RIG-I are members of the evolutionary conserved RIG-like helicase family that play critical roles in the outcome of RNA virus infections. Resolving influenza infection in mammals has been shown to require RIG-I; however, the apparent absence of a RIG-I homolog in chickens raises intriguing questions regarding how this species deals with influenza virus infection. Although chickens are able to resolve certain strains of influenza, they are highly susceptible to others, such as highly pathogenic avian influenza H5N1. Understanding RIG-like helicases in the chicken is of critical importance, especially for developing new therapeutics that may use these systems. With this in mind, we investigated the RIG-like helicase Mda5 in the chicken. We have identified a chicken Mda5 homolog (ChMda5) and assessed its functional activities that relate to antiviral responses. Like mammalian Mda5, ChMda5 expression is upregulated in response to dsRNA stimulation and following IFN activation of cells. Furthermore, RNA interference-mediated knockdown of ChMda5 showed that ChMda5 plays an important role in the IFN response of chicken cells to dsRNA. Intriguingly, although ChMda5 levels are highly upregulated during influenza infection, knockdown of ChMda5 expression does not appear to impact influenza proliferation. Collectively, although Mda5 is functionally active in the chicken, the absence of an apparent RIG-I-like function may contribute to the chicken's susceptibility to highly pathogenic influenza. The Journal of Immunology, 2011, 186: 5397-5405.