Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs:: Implications for latency
Suppression of immediate-early viral gene expression by herpesvirus-coded microRNAs:: Implications for latency
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DOI：
10.1073/pnas.0711910105
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发表时间：
2008-04-08
影响因子：
11.1
通讯作者：
Levine, Arnold J.
中科院分区：
文献类型：
--
作者：
Murphy, Eain;Vanicek, Jiri;Levine, Arnold J.
建立了一种预测疱疹病毒microRNA靶基因的定量算法。虽然不同疱疹病毒亚科的microRNA之间几乎没有保守性，但出现了共同的调控模式。该算法预测，单纯疱疹病毒1型，人类巨细胞病毒，EB病毒和卡波西肉瘤相关疱疹病毒都采用microRNA来抑制其自身基因的表达，包括其立即早期基因。在人巨细胞病毒的情况下，预测病毒编码的微小RNA miR-112-1靶向病毒立即早期蛋白1 mRNA。为了测试这一预测，产生了不能表达microRNA或编码缺乏其靶位点的立即早期1 mRNA的突变病毒。对感染细胞内RNA和蛋白质的分析表明，miR-UL 112 -1抑制了主要立即早期蛋白质的表达。我们认为疱疹病毒使用microRNA介导的立即早期基因抑制作为其进入和维持潜伏期策略的一部分。
A quantitative algorithm was developed and applied to predict target genes of microRNAs encoded by herpesviruses. Although there is almost no conservation among microRNAs of different herpesvirus subfamilies, a common pattern of regulation emerged. The algorithm predicts that herpes simplex virus 1, human cytomegalovirus, Epstein-Barr virus, and Kaposi's sarcoma-associated herpesvirus all employ microRNAs to suppress expression of their own genes, including their immediate-early genes. in the case of human cytomegalovirus, a virus-coded microRNA, miR-112-1, was predicted to target the viral immediate-early protein 1 mRNA. To test this prediction, mutant viruses were generated that were unable to express the microRNA, or encoded an immediate-early 1 mRNA lacking its target site. Analysis of RNA and protein within infected cells demonstrated that miR-UL112-1 inhibits expression of the major immediate-early protein. We propose that herpesviruses use microRNA-mediated suppression of immediate-early genes as part of their strategy to enter and maintain latency.