MDA5 detects the double-stranded RNA replicative form in picornavirus-infected cells.
MDA5 detects the double-stranded RNA replicative form in picornavirus-infected cells.
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DOI：
10.1016/j.celrep.2012.10.005
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发表时间：
2012-11-29
期刊：
影响因子：
8.8
通讯作者：
van Kuppeveld FJ
中科院分区：
文献类型：
--
作者：
Feng Q;Hato SV;Langereis MA;Zoll J;Virgen-Slane R;Peisley A;Hur S;Semler BL;van Rij RP;van Kuppeveld FJ
rig - 1和MDA5是细胞质RNA传感器，在先天抗病毒反应中起关键作用。在鉴定rig - 1配体方面已经取得了重大进展，但我们对MDA5配体的了解仍然局限于主要使用poly(I:C)（一种合成的dsRNA模拟物）转染实验的数据。在这里，我们分析了在小核糖核酸病毒感染过程中，通过RNA转染和在病毒RNA复制的特定步骤被抑制的感染细胞中产生的不同病毒RNA物种的IFN-α/β-刺激活性。我们的研究结果表明，进入基因组的正链RNA不会激活MDA5，但负链RNA的合成和7.5 kbp复制形式的产生会触发强烈的IFN-α/β反应。IFN-α/β的产生不依赖于正链RNA的合成，因此不依赖于部分双链复制中间体的产生。本研究报道了MDA5在生理条件下被天然RNA配体激活。►病毒的ssRNA，无论是否含有5 ' VPg肽，都不会诱导IFN-α/β►负链RNA的合成而不是正链RNA的合成对MDA5的激活至关重要►小核糖核酸RF在体外和体内都能激活MDA5►病毒复制形式对MDA5的激活与该RNA的末端基团无关MDA5是细胞质RNA传感器，在天然抗病毒反应中起关键作用。然而，我们对其配体，特别是生理配体的认识仍然有限。在这里，van Kuppeveld和他的同事们分析了感染过程中产生的不同小核糖核酸RNA物种的mda5刺激活性。它们表明小核糖核酸病毒双链复制形式直接结合并激活MDA5。本研究表明MDA5被天然RNA配体激活。
RIG-I and MDA5 are cytosolic RNA sensors that play a critical role in innate antiviral responses. Major advances have been made in identifying RIG-I ligands, but our knowledge of the ligands for MDA5 remains restricted to data from transfection experiments mostly using poly(I:C), a synthetic dsRNA mimic. Here, we dissected the IFN-α/β-stimulatory activity of different viral RNA species produced during picornavirus infection, both by RNA transfection and in infected cells in which specific steps of viral RNA replication were inhibited. Our results show that the incoming genomic plus-strand RNA does not activate MDA5, but minus-strand RNA synthesis and production of the 7.5 kbp replicative form trigger a strong IFN-α/β response. IFN-α/β production does not rely on plus-strand RNA synthesis and thus generation of the partially double-stranded replicative intermediate. This study reports MDA5 activation by a natural RNA ligand under physiological conditions. ► Viral ssRNA, with or without the 5′ VPg peptide, does not induce IFN-α/β ► Synthesis of minus-strand—but not plus-strand—RNA is crucial for MDA5 activation ► The picornavirus RF activates MDA5 both in vitro and in vivo ► MDA5 activation by viral replicative form is independent of the terminal groups of this RNA MDA5 is a cytosolic RNA sensor and a crucial player in innate antiviral responses. However, our knowledge of its ligands, especially physiological ligands, remains restricted. Here, van Kuppeveld and colleagues dissected the MDA5-stimulatory activity of different picornavirus RNA species produced during infection. They show that the picornavirus double-stranded replicative form directly binds to and activates MDA5. This study shows MDA5 activation by a natural RNA ligand.
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影响因子：
6.7
作者：
McCartney SA;Thackray LB;Gitlin L;Gilfillan S;Virgin HW;Colonna M
通讯作者：
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DOI：
10.1073/pnas.1113651108
发表时间：
2011-12-27
影响因子：
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作者：
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作者：
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通讯作者：
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影响因子：
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作者：
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