Longer and shorter forms of Sendai virus C proteins play different roles in modulating the cellular antiviral response
Longer and shorter forms of Sendai virus C proteins play different roles in modulating the cellular antiviral response
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DOI：
10.1128/jvi.75.15.6800-6807.2001
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发表时间：
2001-08-01
影响因子：
5.4
通讯作者：
Kolakofsky, D
中科院分区：
文献类型：
--
作者：
Garcin, D;Curran, J;Kolakofsky, D
仙台病毒 (SeV) C 基因编码一组嵌套的四种 C 蛋白，这些蛋白执行多种功能，包括调节病毒 RNA 合成和对抗细胞抗病毒反应。使用突变C基因（特别是删除了仅存在于较大C蛋白对中的六个氨基酸的C基因）和携带这些突变C基因的重组SeV，我们发现嵌套的C蛋白组执行一组嵌套的功能。所有 C 蛋白都会阻断干扰素 (IFN) 向 IFN 刺激基因 (ISG) 发出的信号，并阻止 pY701-Stat1 的形成。然而，只有较大的 C 蛋白才能诱导 STAT1 不稳定，阻止 IFN 诱导抗病毒状态，或阻止程序性细胞死亡。值得注意的是，阻断 ISG 的 IFN 信号传导以及 pY701-Stat1 形成的缺失并不能阻止 IFN-α 诱导抗水泡性口炎病毒 (VSV) 状态。诱导抗 VSV 状态的 IFN-α 信号传导可能独立于成熟的 Jak/Stat/ISGF3 途径而发生，并且较长 C 蛋白的目标正是这种平行途径。
The Sendai virus (SeV) C gene codes for a nested set of four C proteins that carry out several functions, including the modulation of viral RNA synthesis and countering of the cellular antiviral response. Using mutant C genes (and in particular a C gene with a deletion of six amino acids present only in the larger pair of C proteins) and recombinant SeV carrying these mutant C genes, we find that the nested set of C proteins carry out a nested set of functions. All of the C proteins interdict interferon (IFN) signaling to IFN-stimulated genes (ISGs) and prevent pY701-Stat1 formation. However, only the larger C proteins can induce STAT1 instability, prevent IFN from inducing an antiviral state, or prevent programmed cell death. Remarkably, interdiction of IFN signaling to ISGs and the absence of pY701-Stat1 formation did not prevent IFN-alpha from inducing an anti-Vesicular stomatitis virus (VSV) state. It is possible that IFN-alpha signaling to induce an anti-VSV state can occur independently of the well-established Jak/Stat/ISGF3 pathway and that it is this parallel pathway that is targeted by the longer C proteins.