Dissection of measles virus V protein in relation to its ability to block alpha/beta interferon signal transduction
Dissection of measles virus V protein in relation to its ability to block alpha/beta interferon signal transduction
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DOI：
10.1099/vir.0.80308-0
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发表时间：
2004-10-01
影响因子：
3.8
通讯作者：
Yanagi, Y
中科院分区：
文献类型：
--
作者：
Ohno, S;Ono, N;Yanagi, Y
干扰素（IFN）-α和-β是针对病毒感染的先天免疫应答的主要细胞因子。为了在宿主中有效地复制，病毒已经进化出针对IFN应答的各种对策。麻疹病毒（MV）的V蛋白已被证明可以阻断IFN-α/β信号传导。在此，MV的野生型IC-B菌株显示在IFN-α存在和不存在下快速生长，而从克隆DNA回收的Edmonston标签菌株的复制在其存在下被强烈抑制。IC-B菌株的V蛋白，而不是Edmonston标签菌株，阻断IFN-α信号传导。来自ATCC的Edmonston菌株的V蛋白也抑制IFN-α信号传导。Edmonston ATCC和标签菌株的V蛋白之间存在三个氨基酸差异，并且Edmonston ATCC V蛋白失去IFN-拮抗剂活性需要在位置110和272处的两个残基的取代。与V蛋白共享N-末端231个氨基酸残基的IC-B菌株的P蛋白也抑制IFN-α信号传导。实际上，仅包含IC-B和Edmonston ATCC V蛋白的那些231个残基而不包含Edmonston标签V蛋白的片段能够阻断IFN-α信号传导。然而，Edmonston标签V蛋白的N-末端区域，当连接到Edmonston ATCC V蛋白的C-末端区域时，抑制IFN-α信号传导。两者合计，我们的研究结果表明，N-和C-末端区域有助于IFN-拮抗剂活性的MV V蛋白。
Interferon (IFN)-alpha and -beta are the main cytokines for innate immune responses against viral infections. To replicate efficiently in the hosts, viruses have evolved various countermeasures to the IFN response. The V protein of measles virus (MV) has been shown to block IFN-alpha/beta signalling. Here, the wild-type IC-B strain of MV was shown to grow comparably in the presence and absence of IFN-alpha, whereas replication of the Edmonston tag strain recovered from cloned DNA was strongly suppressed in its presence. The V protein of the IC-B strain, but not the Edmonston tag strain, blocked IFN-alpha signalling. The V protein of the Edmonston strain from the ATCC also inhibited IFN-alpha signalling. There were three amino acid differences between the V proteins of the Edmonston ATCC and tag strains, and substitutions of both residues at positions 110 and 272 were required for the Edmonston ATCC V protein to lose IFN-antagonist activity. The P protein of the IC-B strain, which shares the N-terminal 231 aa residues with the V protein, also inhibited IFN-alpha signalling. Indeed, fragments comprising only those 231 residues of the IC-B and Edmonston ATCC V proteins, but not the Edmonston tag V protein, were able to block IFN-alpha signalling. However, the N-terminal region of the Edmonston tag V protein, when attached to the C-terminal region of the Edmonston ATCC V protein, inhibited IFN-alpha signalling. Taken together, our results indicate that both the N- and C-terminal regions contribute to the IFN-antagonist activity of the MV V protein.