Dephosphorylation of eIF-2alpha mediated by the gamma(1)34.5 protein of herpes simplex virus type 1 is required for viral response to interferon but is not sufficient for efficient viral replication.
Dephosphorylation of eIF-2alpha mediated by the gamma(1)34.5 protein of herpes simplex virus type 1 is required for viral response to interferon but is not sufficient for efficient viral replication.
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发表时间：
2003
影响因子：
5.4
通讯作者：
G. Cheng;Kui Yang;B. He
中科院分区：
文献类型：
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作者：
G. Cheng;Kui Yang;B. He
单纯疱疹病毒1型(HSV-1) γ(1)34.5蛋白的功能是阻断双链rna依赖性蛋白激酶（PKR）蛋白合成的关闭。在这个过程中，γ(1)34.5蛋白招募细胞蛋白磷酸酶1 （PP1）形成一个高分子量复合物，使eIF-2alpha去磷酸化。在这里，我们证明了γ(1)34.5蛋白能够介导eIF-2alpha去磷酸化，而不需要任何其他病毒蛋白。虽然从gamma(1)34.5蛋白中删除1到52个氨基酸对eIF-2alpha去磷酸化没有影响，但进一步截断至146个氨基酸会显著降低gamma(1)34.5蛋白的活性。氨基酸188的额外截断是有害的，表明羧基末端结构域单独不起作用。与野生型HSV-1一样，截断1至52个氨基酸的γ(1)34.5突变体对干扰素具有抗性，并且对干扰素的抗性与eIF-2alpha去磷酸化偶联。有趣的是，该突变体在感染细胞中表现出与γ(1)34.5零突变体相似的生长缺陷。在重组基因中恢复野生型γ(1)34.5基因完全逆转了表型。这些结果表明，由γ(1)34.5蛋白介导的eIF-2alpha去磷酸化是HSV对干扰素反应所必需的，但对病毒复制并不足够。γ(1)34.5蛋白的其他功能或活性有助于有效的病毒感染。
The gamma(1)34.5 protein of herpes simplex virus type 1 (HSV-1) functions to block the shutoff of protein synthesis involving double-stranded RNA-dependent protein kinase (PKR). In this process, the gamma(1)34.5 protein recruits cellular protein phosphatase 1 (PP1) to form a high-molecular-weight complex that dephosphorylates eIF-2alpha. Here we show that the gamma(1)34.5 protein is capable of mediating eIF-2alpha dephosphorylation without any other viral proteins. While deletion of amino acids 1 to 52 from the gamma(1)34.5 protein has no effect on eIF-2alpha dephosphorylation, further truncations up to amino acid 146 dramatically reduce the activity of the gamma(1)34.5 protein. An additional truncation up to amino acid 188 is deleterious, indicating that the carboxyl-terminal domain alone is not functional. Like wild-type HSV-1, the gamma(1)34.5 mutant with a truncation of amino acids 1 to 52 is resistant to interferon, and resistance to interferon is coupled to eIF-2alpha dephosphorylation. Intriguingly, this mutant exhibits a similar growth defect seen for the gamma(1)34.5 null mutant in infected cells. Restoration of the wild-type gamma(1)34.5 gene in the recombinant completely reverses the phenotype. These results indicate that eIF-2alpha dephosphorylation mediated by the gamma(1)34.5 protein is required for HSV response to interferon but is not sufficient for viral replication. Additional functions or activities of the gamma(1)34.5 protein contribute to efficient viral infection.