Double-stranded RNA binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins
Double-stranded RNA binding by a heterodimeric complex of murine cytomegalovirus m142 and m143 proteins
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DOI：
10.1128/jvi.00905-06
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发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Geballe, Adam P.
中科院分区：
文献类型：
--
作者：
Child, Stephanie J.;Hanson, Laura K.;Geballe, Adam P.
为了应对病毒感染，细胞激活各种抗病毒反应，包括由双链（ds）RNA触发的几种反应。其中包括蛋白激酶R和寡腺苷酸合成酶/ RNase L途径，这两种途径都会导致蛋白质合成的关闭。许多病毒，包括人巨细胞病毒，编码dsRNA结合蛋白，阻止这些途径的激活，从而使持续的蛋白质合成和病毒复制。我们已经将这些分析扩展到疱疹病毒β亚科的另一个成员，鼠巨细胞病毒（MCMV），现在报告说，m142和m143基因的产物一起结合dsRNA。免疫共沉淀实验表明，这两种蛋白质在感染的细胞中相互作用，与它们以前报道的共定位一致。这些蛋白共同而非单独地拯救缺失dsRNA结合蛋白基因E3 L（VV Delta E3 L）的牛痘病毒突变体的复制。与人巨细胞病毒dsRNA结合蛋白基因TRS 1和IRS 1一样，m142和m143也是US 22基因家族的成员。我们还发现MCMV US 22家族的另外两个成员M23和M24编码dsRNA结合蛋白，但它们不能拯救VV Delta E3 L复制。这些结果表明，MCMV，像许多其他病毒，编码dsRNA结合蛋白，其中至少有两个可以抑制dsRNA激活的抗病毒途径。然而，与其他研究充分的例子不同，MCMV蛋白似乎在异二聚体复合物中起作用。
In response to viral infection, cells activate a variety of antiviral responses, including several that are triggered by double-stranded (ds) RNA. Among these are the protein kinase R and oligoadenylate synthetase/ RNase L pathways, both of which result in the shutoff of protein synthesis. Many viruses, including human cytomegalovirus, encode dsRNA-binding proteins that prevent the activation of these pathways and thereby enable continued protein synthesis and viral replication. We have extended these analyses to another member of the beta subfamily of herpesviruses, murine cytomegalovirus (MCMV), and now report that products of the m142 and m143 genes together bind dsRNA. Coimmunoprecipitation experiments demonstrate that these two proteins interact in infected cells, consistent with their previously reported colocalization. Jointly, but not individually, the proteins rescue replication of a vaccinia virus mutant with a deletion of the dsRNA-binding protein gene E3L (VV Delta E3L). Like the human cytomegalovirus dsRNA-binding protein genes TRS1 and IRS1, m142 and m143 are members of the US22 gene family. We also found that two other members of the MCMV US22 family, M23 and M24, encode dsRNA-binding proteins, but they do not rescue VV Delta E3L replication. These results reveal that MCMV, like many other viruses, encodes dsRNA-binding proteins, at least two of which can inhibit dsRNA-activated antiviral pathways. However, unlike other well-studied examples, the MCMV proteins appear to act in a heterodimeric complex.