Adenovirus inhibition of cellular protein synthesis is prevented by the drug 2-aminopurine.
Adenovirus inhibition of cellular protein synthesis is prevented by the drug 2-aminopurine.
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DOI：
10.1073/pnas.87.18.7115
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发表时间：
1990-09
影响因子：
11.1
通讯作者：
J. Huang;R. Schneider
中科院分区：
文献类型：
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作者：
J. Huang;R. Schneider
腺病毒感染导致细胞蛋白质合成受到抑制，但其机制尚未确定。在本报告中，我们证明通过药物 2-氨基嘌呤治疗可以防止细胞中腺病毒对细胞蛋白质合成的阻断。研究表明，2-氨基嘌呤治疗可以防止细胞翻译的抑制，而不会破坏细胞 mRNA 从细胞核到细胞质转运过程中的正常病毒阻断。我们发现，病毒对细胞蛋白质合成的抑制与干扰素诱导的双链RNA激活抑制剂（DAI）（一种蛋白激酶）的激活和真核起始因子2（eIF-2 α）的α亚基的磷酸化同时发生，但2-氨基嘌呤可以防止宿主细胞关闭，而不会降低激酶活性或eIF-2 α去磷酸化。结果表明，DAI 激酶的激活和 eIF-2 α 的磷酸化可能是必需的，但不足以在腺病毒感染期间实现细胞蛋白质合成的抑制。我们认为其他事件，特别是额外起始因子的修饰，可能与病毒对细胞翻译的抑制有关。
Adenovirus infection results in the suppression of cellular protein synthesis, but the mechanism has not been established. In this report we demonstrate that the shut-off of cellular protein synthesis by adenovirus is prevented in cells by treatment with the drug 2-aminopurine. Treatment with 2-aminopurine is shown to prevent suppression of cellular translation without disrupting the normal viral block in the transport of cellular mRNAs from the nucleus to the cytoplasm. We show that viral suppression of cellular protein synthesis occurs concomitant with activation of the interferon-induced double-stranded RNA-activated inhibitor (DAI), a protein kinase, and phosphorylation of the alpha subunit of eukaryotic initiation factor 2 (eIF-2 alpha), but that prevention of host cell shut-off by 2-aminopurine occurs without a decrease in kinase activity or a dephosphorylation of eIF-2 alpha. Results are presented that indicate that activation of DAI kinase and phosphorylation of eIF-2 alpha may be required but are not sufficient to achieve inhibition of cellular protein synthesis during adenovirus infection. We suggest that other events, in particular the modification of additional initiation factors, are likely involved in viral inhibition of cellular translation.