Measles Virus Nonstructural C Protein Modulates Viral RNA Polymerase Activity by Interacting with Host Protein SHCBP1
Measles Virus Nonstructural C Protein Modulates Viral RNA Polymerase Activity by Interacting with Host Protein SHCBP1
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DOI：
10.1128/jvi.00714-13
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发表时间：
2013-09-01
影响因子：
5.4
通讯作者：
Ohno, Shinji
中科院分区：
文献类型：
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作者：
Ito, Minako;Iwasaki, Masaharu;Ohno, Shinji
大多数病毒都有规避宿主免疫反应的策略。麻疹病毒（MV）的非结构性C蛋白抑制干扰素反应，从而使有效的病毒生长，但其详细的机制一直是未知的。我们确定Shc Src同源2域结合蛋白1（SHCBP1）作为与C蛋白相互作用的宿主蛋白之一。使用短发夹RNA敲低SHCBP1大大降低了MV的生长。SHCBP1被发现是所需的病毒RNA合成的微型基因组检测和结合MV磷蛋白，病毒RNA聚合酶的亚基。C蛋白中12个氨基酸残基的延伸足以与SHCBP 1结合，并且含有这12个残基的肽可以抑制MV RNA的合成，就像全长C蛋白一样。SHCBP1的中心区域被发现与C蛋白以及磷蛋白结合，但这两种病毒蛋白不竞争SHCBP1结合。我们的研究结果表明，C蛋白调节MV RNA聚合酶的活性结合宿主蛋白SHCBP1。SHCBP1可以作为抗病毒化合物的靶点。
Most viruses possess strategies to circumvent host immune responses. The measles virus (MV) nonstructural C protein suppresses the interferon response, thereby allowing efficient viral growth, but its detailed mechanism has been unknown. We identified Shc Src homology 2 domain-binding protein 1 (SHCBP1) as one of the host proteins interacting with the C protein. Knockdown of SHCBP1 using a short-hairpin RNA greatly reduced MV growth. SHCBP1 was found to be required for viral RNA synthesis in the minigenome assay and to bind to the MV phosphoprotein, a subunit of the viral RNA polymerase. A stretch of 12 amino acid residues in the C protein were sufficient for SHCBP1 binding, and the peptide containing these 12 residues could suppress MV RNA synthesis, like the full-length C protein. The central region of SHCBP1 was found to bind to the C protein, as well as the phosphoprotein, but the two viral proteins did not compete for SHCBP1 binding. Our results indicate that the C protein modulates MV RNA polymerase activity by binding to the host protein SHCBP1. SHCBP1 may be exploited as a target of antiviral compounds.