Inhibition of IFN-α/β signaling by two discrete peptides within measles virus V protein that specifically bind STAT1 and STAT2
Inhibition of IFN-α/β signaling by two discrete peptides within measles virus V protein that specifically bind STAT1 and STAT2
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DOI：
10.1016/j.virol.2008.10.014
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发表时间：
2009-01-05
期刊：
影响因子：
3.7
通讯作者：
Vidalain, Pierre-Olivier
中科院分区：
文献类型：
--
作者：
Caignard, Gregory;Bourai, Mehdi;Vidalain, Pierre-Olivier
麻疹病毒V蛋白(MV-V)是干扰素-α/β信号通路的有效抑制因子。我们以前报道过，当MV-V的N-末端和C-末端区域(分别是PNT和VCT)物理分离时，可以独立地削弱信号转导。PNT区通过与该途径的至少两个组成部分JAK1和STAT1相互作用来抑制干扰素-α/β信号。在这里，我们报道了MV-V的VCT与干扰素-α/β转导机制的第三组分STAT2之间的直接相互作用。这种与STAT2的相互作用是由位于VCT区域的49个氨基酸组成的半胱氨酸限制性多肽携带的，对于抑制干扰素-α/β信号是必不可少的。同时，我们还在PNT区域定位了STAT1结合位点，并确定了一个仅由I I氨基酸组成的最小多肽。用融合到细胞穿透序列的MV-V多肽处理的人细胞中，干扰素-α/β信号受到损害。最后，我们证明了干扰素-lambda下游的信号传递被MV-V阻断，干扰素-lambda是最近发现的一种细胞因子，也依赖于STAT1、STAT2和JAK1进行转导。总之，我们的结果说明了单一病毒蛋白是如何进化到通过与几个信号分子相互作用来实现对抗病毒反应的强大抑制的。(C)2008 Elsevier Inc.保留所有权利。
The V protein of measles virus (MV-V) is a potent inhibitor of IFN-alpha/beta signaling pathway. We previously reported that when physically dissociated, the N-terminal and C-terminal regions of MV-V (PNT and VCT, respectively) Could independently impair signal transduction. The PNT region inhibited IFN-alpha/beta signaling by interacting with at least two components of this pathway: Jak1 and STAT1. Here we report a direct interaction between the VCT of MV-V and STAT2, a third component of IFN-alpha/beta transduction machinery. This interaction with STAT2 is carried by the cysteine-constrained peptide of 49 amino acids localized in the VCT region, and is essential to the inhibition of IFN-alpha/beta signaling. In parallel, we also mapped STAT1 binding site in the PNT region and identified a minimal peptide of only I I amino acids. IFN-alpha/beta signaling was impaired in human cells treated with this MV-V peptide fused to a cell-penetrating sequence. Finally, we show that signaling downstream of IFN-lambda, a recently identified cytokine that also relies on STAT1, STAT2 and Jak1 to transduce, is blocked by MV-V. Altogether, our results illustrate how a single viral protein has evolved to achieve a robust inhibition of the antiviral response by interacting with several signaling molecules. (c) 2008 Elsevier Inc. All rights reserved.