Semliki forest virus nonstructural protein 2 is involved in suppression of the type I interferon response
Semliki forest virus nonstructural protein 2 is involved in suppression of the type I interferon response
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DOI：
10.1128/jvi.02411-06
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发表时间：
2007-08-01
影响因子：
5.4
通讯作者：
McInerney, Gerald M.
中科院分区：
文献类型：
--
作者：
Breakwell, Lucy;Dosenovic, Pia;McInerney, Gerald M.
I型干扰素（IFN）是抗病毒免疫的有效介质，并且许多病毒已经开发出阻断其表达或其作用的方法。塞姆利基森林病毒（SFV）感染诱导宿主细胞基因表达的快速和深刻的沉默，这一过程被认为是重要的IFN反应的抑制。在SFV感染的细胞中，发现大部分非结构蛋白nsp 2位于细胞核中，但这种定位的作用尚未被描述。在这项工作中，我们证明了一种病毒突变体，SFV 4-RDR，其中nsp 2的核定位序列已被赋予无活性，诱导感染细胞中的IFN反应显着更强大。该突变病毒以与亲本SFV 4株相似的速率复制，并且也将宿主细胞基因表达关闭至相似的水平，这表明一般细胞关闭不负责IFN表达的抑制。此外，未发现病毒诱导的早期IFN转录因子核转位速率在野生型和突变型病毒之间存在差异，表明nsp 2的作用处于后期阶段。这些结果提供了新的信息，这种病毒干扰素拮抗剂的作用方式。
The type I interferons (IFNs) are potent mediators of antiviral immunity, and many viruses have developed means to block their expression or their effects. Semliki Forest virus (SFV) infection induces rapid and profound silencing of host cell gene expression, a process believed to be important for the inhibition of the IFN response. In SFV-infected cells, a large proportion of the nonstructural protein nsp2 is found in the nucleus, but a role for this localization has not been described. In this work we demonstrate that a viral mutant, SFV4-RDR, in which the nuclear localization sequence of nsp2 has been rendered inactive, induces a significantly more robust IFN response in infected cells. This mutant virus replicates at a rate similar to that of the parental SFV4 strain and also shuts off host cell gene expression to similar levels, indicating that the general cellular shutoff is not responsible for the inhibition of IFN expression. Further, the rate of virus-induced nuclear translocation of early IFN transcription factors was not found to differ between the wild-type and mutant viruses, indicating that the effect of nsp2 is at a later stage. These results provide novel information about the mode of action of this viral IFN antagonist.