The VSV matrix protein inhibits NF-κB and the interferon response independently in mouse L929 cells
The VSV matrix protein inhibits NF-κB and the interferon response independently in mouse L929 cells
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DOI：
10.1016/j.virol.2020.06.013
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发表时间：
2020-09-01
期刊：
影响因子：
3.7
通讯作者：
Ferran, Maureen C.
中科院分区：
文献类型：
--
作者：
Marquis, Kaitlin A.;Becker, Rachel L.;Ferran, Maureen C.
水泡性口炎病毒（VSV）的基质（M）蛋白在免疫逃避中起着关键作用。虽然VSV被认为主要通过抑制宿主细胞转录和翻译来抑制干扰素（IFN）应答，但我们最近的研究结果表明M蛋白也靶向NF-κ B活化。因此，M蛋白可能利用两种不同的机制来限制抗病毒基因的表达，抑制宿主基因表达和NF-κ B活化。在这里，我们描述了最近报道的VSV分离株22-20的M蛋白[M（D52 G）]突变，该突变抑制了IFN mRNA和蛋白的产生，尽管激活了NF-κ B。22-20抑制来自多个启动子的报告基因表达，表明22-20通过M介导的宿主细胞转录抑制而抑制IFN应答。我们认为IFN应答的抑制和NF-κ B的调节是VSV M蛋白的独立的、遗传上可分离的功能。
The matrix (M) protein of vesicular stomatitis virus (VSV) plays a key role in immune evasion. While VSV has been thought to suppress the interferon (IFN) response primarily by inhibiting host cell transcription and translation, our recent findings indicate that the M protein also targets NF-kappa B activation. Therefore, the M protein may utilize two distinct mechanisms to limit expression of antiviral genes, inhibiting both host gene expression and NF-kappa B activation. Here we characterize a recently reported mutation in the M protein [M(D52G)] of VSV isolate 22-20, which suppressed IFN mRNA and protein production despite activating NF-kappa B. 22-20 inhibited reporter gene expression from multiple promoters, suggesting that 22-20 suppressed the IFN response via M-mediated inhibition of host cell transcription. We propose that suppression of the IFN response and regulation of NF-kappa B are independent, genetically separable functions of the VSV M protein.