Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways.

Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways.
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DOI:
10.1371/journal.pone.0057063
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Baron MD
Baron MD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chinnakannan SK;Nanda SK;Baron MD

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麻疹病毒是一组密切相关的致病性病毒,在其P基因中编码三种非结构蛋白V、W和C。先前对牛瘟病毒(RPV)和麻疹病毒(MeV)的研究已经证明,这些非结构蛋白在阻断I型(IFNα/β)和II型(IFNγ)干扰素作用中起关键作用,并且已经提出了这些作用的各种机制。我们直接比较了牛瘟病毒(RPV)、麻疹病毒(MeV)、小反刍兽疫病毒(PPRV)和犬瘟热病毒(CDV)四种重要的麻疹病毒。这些病毒和它们的V蛋白都可以阻断I型IFN的作用。然而,病毒和它们的V蛋白具有不同的能力来阻断II型IFN的作用。阻断II型IFN诱导的基因转录的能力与STAT 1与各自的V蛋白的共沉淀相关,但STAT 1或STAT 2的共沉淀与V蛋白阻断I型IFN诱导的基因转录或产生抗病毒状态的能力之间没有相关性。进一步的研究表明,RPV、MeV、PPRV和CDV的V蛋白均能干扰素受体相关激酶Tyk 2的磷酸化,强毒力RPV的V蛋白还能阻断另一种干扰素受体相关激酶Jak 1的磷酸化。共沉淀研究表明,麻疹病毒V蛋白都形成一个含有Tyk 2和Jak 1的复合物。这项研究突出了麻疹病毒V蛋白的能力,以目标的IFN信号通路的多个组件,以控制I型和II型IFN的行动。
Morbilliviruses form a closely related group of pathogenic viruses which encode three non-structural proteins V, W and C in their P gene. Previous studies with rinderpest virus (RPV) and measles virus (MeV) have demonstrated that these non-structural proteins play a crucial role in blocking type I (IFNα/β) and type II (IFNγ) interferon action, and various mechanisms have been proposed for these effects. We have directly compared four important morbilliviruses, rinderpest (RPV), measles virus (MeV), peste des petits ruminants virus (PPRV) and canine distemper virus (CDV). These viruses and their V proteins could all block type I IFN action. However, the viruses and their V proteins had varying abilities to block type II IFN action. The ability to block type II IFN-induced gene transcription correlated with co-precipitation of STAT1 with the respective V protein, but there was no correlation between co-precipitation of either STAT1 or STAT2 and the abilities of the V proteins to block type I IFN-induced gene transcription or the creation of the antiviral state. Further study revealed that the V proteins of RPV, MeV, PPRV and CDV could all interfere with phosphorylation of the interferon-receptor-associated kinase Tyk2, and the V protein of highly virulent RPV could also block the phosphorylation of another such kinase, Jak1. Co-precipitation studies showed that morbillivirus V proteins all form a complex containing Tyk2 and Jak1. This study highlights the ability of morbillivirus V proteins to target multiple components of the IFN signalling pathways to control both type I and type II IFN action.
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