病毒感染中MDA5的细胞因子非依赖性上调
Cytokine-independent upregulation of MDA5 in viral infection.
作者信息
Yount Jacob S, Moran Thomas M, López Carolina B
机构信息
Department of Microbiology, The Mount Sinai School of Medicine, One Gustave L. Levy Place, Box 1124, New York, NY 10029, USA.
出版信息
J Virol. 2007 Jul;81(13):7316-9. doi: 10.1128/JVI.00545-07. Epub 2007 May 2.
Abstract
The RNA helicases RIG-I and MDA5 detect virus infection of dendritic cells (DCs) leading to cytokine induction. Maximal sensitivity for virus detection by these helicases is obtained after their upregulation, which is thought to occur primarily through type I interferon (IFN) signaling. Here we demonstrate that in response to paramyxovirus infection, RIG-I upregulation requires type I IFN whereas MDA5 expression is increased by Sendai virus infection independently of signaling mediated by type I IFN, STAT1, tumor necrosis factor alpha, or NF-kappaB. This MDA5 upregulation is largely lost in IRF3 knockout DCs and is achieved in type I IFN-deficient cells expressing constitutively active IRF3.
摘要
RNA解旋酶RIG-I和MDA5可检测树突状细胞（DC）的病毒感染，从而诱导细胞因子产生。这些解旋酶在表达上调后，对病毒检测的敏感性达到最高，而这种上调被认为主要通过I型干扰素（IFN）信号传导发生。在此我们证明，在应对副粘病毒感染时，RIG-I的上调需要I型干扰素，而仙台病毒感染可使MDA5表达增加，且这一过程不依赖于I型干扰素、STAT1、肿瘤坏死因子α或核因子κB介导的信号传导。这种MDA5的上调在IRF3基因敲除的DC中基本消失，而在表达组成型活性IRF3的I型干扰素缺陷细胞中则可实现。
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