Measles virus suppresses interferon-α signaling pathway:: suppression of Jak1 phosphorylation and association of viral accessory proteins, C and V, with interferon-α receptor complex
Measles virus suppresses interferon-α signaling pathway:: suppression of Jak1 phosphorylation and association of viral accessory proteins, C and V, with interferon-α receptor complex
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DOI：
10.1016/s0042-6822(02)00026-0
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发表时间：
2003-02-01
期刊：
影响因子：
3.7
通讯作者：
Fujii, N
中科院分区：
文献类型：
--
作者：
Yokota, S;Saito, H;Fujii, N
为了建立感染，病毒使用各种策略来抑制宿主防御机制，例如干扰素 (IFN) 诱导的抗病毒状态。我们发现，感染麻疹病毒野生株（MeV）的细胞表现出几乎完全抑制 IFN-α 诱导的抗病毒状态，但不是 IFN-γ 诱导的状态。这种现象是由于转录水平上 IFN-α 诱导基因表达的抑制所致。在IFN-α信号转导途径中，在MeV感染的细胞中，IFN-α诱导的Jak1磷酸化被显着抑制；然而，IFN-γ 诱导的磷酸化则不然。我们使用针对 1 型 IFN 受体链 1 (INFAR1) 的抗体和针对 RACK1 的抗体进行了免疫沉淀实验，据报道，RACK1 是与 I 型 IFN 受体链 2 和 STAT1 相互作用的支架蛋白。这些实验表明，IFNAR1 在 MeV 感染的细胞中形成包含 MeV 辅助蛋白 C 和 V、RACK1 和 STAT 的复合物，但在未感染的细胞中则不然。 IFN-α 处理后，受感染细胞中该复合物的组成几乎没有改变。这些结果表明 MeV 通过抑制 Jak1 磷酸化来抑制 IFN-α 信号通路，但不抑制 IFN-γ 信号通路。我们的数据表明，I 型 IFN 受体复合物的功能障碍是由于受体通过与 MeV 的 C 和/或 V 蛋白结合而“冻结”所致。 (C) 2003 年爱思唯尔科学（美国）。版权所有。
To establish infections, viruses use various strategies to suppress the host defense mechanism, such as interferon (IFN)-induced antiviral state. We found that cells infected with a wild strain of measles virus (MeV) displayed nearly complete suppression of IFN-alpha-induced antiviral state, but not IFN-gamma-induced state. This phenomenon is due to the suppression of IFN-alpha-inducible gene expression at a transcriptional level. In the IFN-alpha signal transduction pathway, Jak1 phosphorylation induced by IFN-alpha is dramatically suppressed in MeV-infected cells; however, phosphorylation induced by IFN-gamma is not. We performed immunoprecipitation experiments using antibodies against type 1 IFN receptor chain 1 (INFAR1) and antibody against RACK1, which is reported to be a scaffold protein interacting with type I IFN receptor chain 2 and STAT1. These experiments indicated that IFNAR1 forms a complex containing the MeV-accessory proteins C and V, RACK1, and STAT in MeV-infected cells but not in uninfected cells. Composition of this complex in the infected cells altered little by IFN-alpha treatment. These results indicate that MeV suppresses the IFN-alpha, but not IFN-gamma, signaling pathway by inhibition of Jak1 phosphorylation. Our data suggest that functional disorder of the type I IFN receptor complex is due to "freezing" of the receptor through its association with the C and/or V proteins of MeV. (C) 2003 Elsevier Science (USA). All rights reserved.