Antagonism of the phosphatase PP1 by the measles virus V protein is required for innate immune escape of MDA5.
Antagonism of the phosphatase PP1 by the measles virus V protein is required for innate immune escape of MDA5.
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DOI：
10.1016/j.chom.2014.06.007
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发表时间：
2014-07-09
影响因子：
30.3
通讯作者：
Gack MU
中科院分区：
文献类型：
--
作者：
Davis ME;Wang MK;Rennick LJ;Full F;Gableske S;Mesman AW;Gringhuis SI;Geijtenbeek TB;Duprex WP;Gack MU
胞质传感器MDA 5对于针对包括麻疹病毒在内的各种RNA病毒的抗病毒先天免疫防御至关重要;因此，许多病毒已经进化出拮抗MDA 5的抗病毒活性的策略。在这里，我们发现麻疹病毒通过靶向磷酸酶PP 1 α和PP 1 γ逃避MDA 5检测，磷酸酶PP 1 α和PP 1 γ通过去除抑制性磷酸化标记来调节MDA 5活性。麻疹病毒和相关副粘病毒尼帕病毒的V蛋白与PP 1 α/γ相互作用，阻止PP 1介导的MDA 5去磷酸化，从而阻止其活化。PP 1与麻疹V蛋白的相互作用是由V蛋白C-末端区域中保守的PP 1结合基序介导的。表达PP 1结合缺陷的突变V蛋白的重组麻疹病毒不能拮抗MDA 5，并且由于其不能抑制干扰素诱导而生长受损。这确定PP 1拮抗作用是副粘病毒逃避先天免疫识别的机制。
The cytosolic sensor MDA5 is crucial for antiviral innate immune defense against various RNA viruses including measles virus; as such, many viruses have evolved strategies to antagonize the antiviral activity of MDA5. Here, we show that measles virus escapes MDA5 detection by targeting the phosphatases PP1α and PP1γ, which regulate MDA5 activity by removing an inhibitory phosphorylation mark. The V proteins of measles virus and the related paramyxovirus Nipah virus interact with PP1α/γ, preventing PP1-mediated dephosphorylation of MDA5 and thereby its activation. The PP1 interaction with the measles V protein is mediated by a conserved PP1-binding motif in the C-terminal region of the V protein. A recombinant measles virus expressing a mutant V protein deficient in PP1 binding is unable to antagonize MDA5 and is growth-impaired due to its inability to suppress interferon induction. This identifies PP1 antagonism as a mechanism employed by paramyxoviruses for evading innate immune recognition.
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影响因子：
32.4
作者：
Loo YM;Gale M Jr
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DOI：
10.1074/jbc.m109.089912
发表时间：
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期刊：
The Journal of biological chemistry
影响因子：
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