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布尼亚姆韦拉正布尼亚病毒NSs蛋白与中介蛋白MED8的相互作用:一种抑制干扰素反应的机制

Interaction of Bunyamwera Orthobunyavirus NSs protein with mediator protein MED8: a mechanism for inhibiting the interferon response.

作者信息

Léonard Vincent H J, Kohl Alain, Hart Timothy J, Elliott Richard M

机构信息

Division of Virology, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow G11 5JR, Scotland, United Kingdom.

出版信息

J Virol. 2006 Oct;80(19):9667-75. doi: 10.1128/JVI.00822-06.

Abstract

The NSs protein of Bunyamwera virus (Bunyaviridae) is an antiapoptotic interferon antagonist involved in silencing host protein expression by interfering with mRNA synthesis. Here, we show that the ability to inhibit both host transcription and the interferon response is linked to interaction of NSs with the MED8 component of Mediator, a protein complex necessary for mRNA production. The interacting domain on NSs was mapped to the C-terminal region, which contains amino acids conserved among orthobunyavirus NSs proteins. A recombinant virus in which the interacting domain in NSs was deleted had strongly reduced ability to inhibit host protein expression and was unable to inhibit the interferon response. This study provides further information on the mechanisms by which bunyavirus nonstructural proteins are involved in pathogenesis.

摘要

布尼亚姆韦拉病毒(布尼亚病毒科)的NSs蛋白是一种抗凋亡干扰素拮抗剂,通过干扰mRNA合成参与沉默宿主蛋白表达。在此,我们表明,抑制宿主转录和干扰素反应的能力与NSs与中介体的MED8组分相互作用有关,中介体是mRNA产生所必需的一种蛋白复合物。NSs上的相互作用结构域定位于C末端区域,该区域包含正布尼亚病毒NSs蛋白中保守的氨基酸。缺失NSs中相互作用结构域的重组病毒抑制宿主蛋白表达的能力大幅降低,且无法抑制干扰素反应。本研究提供了关于布尼亚病毒非结构蛋白参与发病机制的更多信息。

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