Ebola Virus VP35 Antagonizes PKR Activity through Its C-Terminal Interferon Inhibitory Domain
Ebola Virus VP35 Antagonizes PKR Activity through Its C-Terminal Interferon Inhibitory Domain
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DOI：
10.1128/jvi.00523-09
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发表时间：
2009-09-01
影响因子：
5.4
通讯作者：
Muehlberger, Elke
中科院分区：
文献类型：
--
作者：
Schuemann, Michael;Gantke, Thorsten;Muehlberger, Elke
埃博拉病毒VP35含有双链RNA（dsRNA）结合和抑制干扰素调节因子3（IRF3）所需的碱性氨基酸的C末端簇。VP35也阻断蛋白激酶R（PKR）的激活，然而，负责的结构域仍然不确定。在这里，我们表明，IRF抑制结构域的VP35介导的PKR的抑制，并增强共表达蛋白的合成。与dsRNA结合和IRF抑制相反，需要至少两个碱性氨基酸的丙氨酸取代来消除PKR抑制和增强蛋白质表达。此外，我们发现PKR激活不仅被阻断，而且被埃博拉病毒感染逆转。
Ebola virus VP35 contains a C-terminal cluster of basic amino acids required for double-stranded RNA ( dsRNA) binding and inhibition of interferon regulatory factor 3 (IRF3). VP35 also blocks protein kinase R (PKR) activation; however, the responsible domain has remained undefined. Here we show that the IRF inhibitory domain of VP35 mediates the inhibition of PKR and enhances the synthesis of coexpressed proteins. In contrast to dsRNA binding and IRF inhibition, alanine substitutions of at least two basic amino acids are required to abrogate PKR inhibition and enhanced protein expression. Moreover, we show that PKR activation is not only blocked but reversed by Ebola virus infection.