Department of Virology, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
J Virol. 2013 Sep;87(17):9633-42. doi: 10.1128/JVI.00714-13. Epub 2013 Jun 26.
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.
大多数病毒都有策略来规避宿主的免疫反应。麻疹病毒（MV）的非结构 C 蛋白抑制干扰素反应，从而允许病毒高效生长，但其详细机制尚不清楚。我们鉴定出 Shc Src 同源 2 结构域结合蛋白 1（SHCBP1）是与 C 蛋白相互作用的宿主蛋白之一。使用短发夹 RNA 敲低 SHCBP1 会大大降低 MV 的生长。在小基因组测定中发现 SHCBP1 是病毒 RNA 合成所必需的，并且与 MV 磷蛋白结合，磷蛋白是病毒 RNA 聚合酶的一个亚基。C 蛋白中 12 个氨基酸残基的一段序列足以与 SHCBP1 结合，并且包含这 12 个残基的肽可以像全长 C 蛋白一样抑制 MV RNA 合成。发现 SHCBP1 的中心区域与 C 蛋白以及磷蛋白结合，但这两种病毒蛋白不竞争 SHCBP1 结合。我们的结果表明，C 蛋白通过与宿主蛋白 SHCBP1 结合来调节 MV RNA 聚合酶的活性。SHCBP1 可能被用作抗病毒化合物的靶标。
