Measles virus circumvents the host interferon response by different actions of the C and V proteins
Measles virus circumvents the host interferon response by different actions of the C and V proteins
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DOI：
10.1128/jvi.00108-08
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发表时间：
2008-09-01
影响因子：
5.4
通讯作者：
Yanagi, Yusuke
中科院分区：
文献类型：
--
作者：
Nakatsu, Yuichiro;Takeda, Makoto;Yanagi, Yusuke
麻疹是一种急性发热性传染病，发病率和死亡率都很高。麻疹病毒（MV）的基因组编码两种辅助产物V蛋白和C蛋白，它们在MV的毒力中起重要作用。已显示IC-B株（MV的充分表征的强毒株）的V而非C蛋白阻断Jak/Stat信号传导途径并抵消细胞干扰素（IFN）应答。我们最近发现，缺乏C蛋白表达的重组IC-B菌株在某些细胞系中复制较差，其生长缺陷与翻译抑制和强IFN诱导有关。在这里，我们表明，V蛋白的MV IC-B株也阻断了IFN诱导途径介导的黑色素瘤分化相关基因5的产品，从而积极干扰宿主IFN反应在两个不同的步骤。另一方面，C蛋白本身不具有阻断IFN诱导途径的活性。我们的数据表明，C蛋白作为病毒RNA合成的调节剂，从而间接抑制IFN诱导。由于C蛋白在调节病毒RNA合成中有缺陷或缺乏C蛋白表达的重组MV强烈刺激IFN产生，尽管V蛋白产生，但MV必须需要C和V蛋白以完全规避宿主IFN应答。
Measles is an acute febrile infectious disease with high morbidity and mortality. The genome of measles virus (MV), the causative agent, encodes two accessory products, V and C proteins, that play important roles in MV virulence. The V but not the C protein of the IC-B strain (a well-characterized virulent strain of MV) has been shown to block the Jak/Stat signaling pathway and counteract the cellular interferon (IFN) response. We have recently shown that a recombinant IC-B strain that lacks C protein expression replicates poorly in certain cell lines, and its growth defect is related to translational inhibition and strong IFN induction. Here, we show that the V protein of the MV IC-B strain also blocks the IFN induction pathway mediated by the melanoma differentiation-associated gene 5 product, thus actively interfering with the host IFN response at two different steps. On the other hand, the C protein per se possesses no activity to block the IFN induction pathway. Our data indicate that the C protein acts as a regulator of viral RNA synthesis, thereby acting indirectly to suppress IFN induction. Since recombinant MVs with C protein defective in modulating viral RNA synthesis or lacking C protein expression strongly stimulate IFN production, in spite of V protein production, both the C and V proteins must be required for MV to fully circumvent the host IFN response.