Analysis of interaction of Sendai virus V protein and melanoma differentiation-associated gene 5
Analysis of interaction of Sendai virus V protein and melanoma differentiation-associated gene 5
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仙台病毒V蛋白与黑色素瘤分化相关基因5的相互作用分析
DOI：
10.1111/j.1348-0421.2011.00379.x
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发表时间：
2011
影响因子：
2.6
通讯作者：
R. Kawabata
中科院分区：
文献类型：
--
作者：
Sakaguchi;T.;T. Irie;M. Kuwayama;T. Ueno;A. Yoshida;R. Kawabata
仙台病毒（SeV）是一种啮齿动物嗜肺病毒，具有辅助蛋白V，并且V蛋白已被证明与MDA 5相互作用，抑制IRF 3活化和干扰素-β产生。在本研究中，在免疫共沉淀试验中研究了V蛋白与各种IRF 3激活蛋白（包括MDA 5）的相互作用。我们还研究了来自低致病性SeV的突变V蛋白与MDA 5的相互作用。V蛋白至少与视黄酸诱导基因I、κB激酶抑制剂κB和IRF 3相互作用，而不与MDA 5相互作用。然而，只有MDA 5依赖于C末端V独特（Vu）区域与V蛋白相互作用，抑制IRF 3报告基因激活。Vu区已被证明是重要的病毒致病性。因此，我们专注于V蛋白与MDA 5的相互作用。Vu区的点突变使V蛋白不稳定或在V蛋白稳定时消除与MDA 5的相互作用。V-R320 G蛋白是高度稳定的并且与MDA 5相互作用，但不抑制由MDA 5诱导的IRF 3的活化。SeV的致病性与V蛋白对MDA 5的抑制作用有关，但并不总是与V蛋白与MDA 5的结合有关。
Sendai virus (SeV), a pneumotropic virus of rodents, has an accessory protein, V, and the V protein has been shown to interact with MDA5, inhibiting IRF3 activation and interferon‐β production. In the present study, interaction of the V protein with various IRF3‐activating proteins including MDA5 was investigated in a co‐immunoprecipitation assay. We also investigated interaction of mutant V proteins from SeVs of low pathogenicity with MDA5. The V protein interacted with at least retinoic acid inducible gene I, inhibitor of κB kinase epsilon and IRF3 other than MDA5. However, only MDA5 interacted with the V protein dependently on the C‐terminal V unique (Vu) region, inhibiting IRF3 reporter activation. The Vu region has been shown to be important for viral pathogenicity. We thus focused on interaction of the V protein with MDA5. Point mutations in the Vu region destabilized the V protein or abolished the interaction with MDA5 when the V protein was stable. The V‐R320G protein was highly stable and interacted with MDA5, but did not inhibit activation of IRF3 induced by MDA5. Viral pathogenicity of SeV is related to the inhibitory effect of the V protein on MDA5, but is not always related to the binding of V protein with MDA5.