PROCESSING OF THE HERPES-SIMPLEX VIRUS REGULATORY PROTEIN ALPHA-22 MEDIATED BY THE U(L)13 PROTEIN-KINASE DETERMINES THE ACCUMULATION OF A SUBSET OF ALPHA-MESSENGER RNAS AND GAMMA-MESSENGER RNAS AND PROTEINS IN INFECTED-CELLS
PROCESSING OF THE HERPES-SIMPLEX VIRUS REGULATORY PROTEIN ALPHA-22 MEDIATED BY THE U(L)13 PROTEIN-KINASE DETERMINES THE ACCUMULATION OF A SUBSET OF ALPHA-MESSENGER RNAS AND GAMMA-MESSENGER RNAS AND PROTEINS IN INFECTED-CELLS
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DOI：
10.1073/pnas.90.14.6701
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发表时间：
1993-07-15
影响因子：
11.1
通讯作者：
ROIZMAN, B
中科院分区：
文献类型：
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作者：
PURVES, FC;OGLE, WO;ROIZMAN, B
我们先前报道过与单纯疱疹病毒1型感染细胞蛋白22(ICP22)的磷酸化相关的翻译后加工是由编码病毒粒子结构蛋白的基因U(L)13编码的。我们现在报道以下内容。(I)在感染缺乏U(L)13(DELTAU(L)13)突变体的细胞中，限制性感染细胞积累了水平降低的调节蛋白ICPO和几种晚期病毒蛋白。在感染编码ICP22的突变株(DELTAalpha22)的同一细胞系中也观察到相同的减少。我们的结论是，U(L)13介导的ICP22的加工是其基因调控功能所必需的。(Ii)感染DELTAU(L)13或DELTAalpha22病毒的细胞中特定病毒蛋白积累的减少与ICPO和受影响的晚期基因的特定mRNAs水平的降低有关。(3)ICP22在感染过程中不被细胞内的U(L)13蛋白修饰。(4)U(S)3编码的蛋白激酶也对ICP22进行修饰，但这种修饰不同于U(L)13编码的蛋白激酶。这些结果预测UL13编码一种蛋白激酶或磷酸转移酶，它在复制生命周期的后期表达，直接或间接地使ICP22磷酸化。这种修饰对于稳定或增加特定的病毒RNA亚集的转录，最终对相应病毒蛋白的积累是必不可少的。
We reported previously that the posttranslational processing associated with phosphorylation of the herpes simplex virus 1 infected-cell protein 22 (ICP22), a regulatory protein, is encoded by U(L)13, a gene encoding a structural protein of the virion. We now report the following. (i) In cells infected with a mutant lacking U(L)13 (DELTAU(L)13), restricted infected cells accumulate reduced levels of the regulatory protein ICPO and several late viral proteins. Identical reductions have been observed in the same cell lines infected with a mutant from which the alpha22 gene, encoding ICP22, had been deleted (DELTAalpha22). We conclude that the U(L)13-mediated processing of ICP22 is essential for its gene-regulatory function. (ii) The reduced accumulations of specific viral protein in cells infected with either DELTAU(L)13 or DELTAalpha22 viruses correlate with reduced levels of specific mRNAs for both ICPO and the affected late genes. (iii) ICP22 is not modified by the U(L)13 protein introduced into cells during infection. (iv) ICP22 is also modified by the protein kinase encoded by U(S)3, but this modification is different from that of the U(L)13 protein kinase. These results predict that UL13 encodes a protein kinase or phosphotransferase which is expressed late in the replicative life cycle and which directly or indirectly phosphorylates ICP22. This modification is essential for stabilization or increased transcription of a specific subset of viral RNAs and, ultimately, for the accumulation of corresponding viral proteins.