ORF18 is a transfactor that is essential for late gene transcription of a gammaherpesvirus
ORF18 is a transfactor that is essential for late gene transcription of a gammaherpesvirus
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DOI：
10.1128/jvi.00246-06
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发表时间：
2006-10-01
影响因子：
5.4
通讯作者：
Sun, Ren
中科院分区：
文献类型：
--
作者：
Arumugaswami, Vaithilingaraja;Wu, Ting-Ting;Sun, Ren
肿瘤相关的人γ疱疹病毒、EB病毒和卡波西肉瘤相关疱疹病毒的裂解性复制在发病机制和肿瘤发生中具有重要意义。疱疹病毒裂解基因在时间上被分类为表现出立即早期（IE）、早期和晚期表达动力学。虽然IE和早期基因表达的调节已经被广泛研究，但关于晚期基因表达的调节知之甚少。晚期基因主要编码病毒粒子结构蛋白，需要病毒DNA复制才能表达。我们已经确定了小鼠γ疱疹病毒68（MRV-68）的早期裂解基因，ORF 18，病毒复制所必需的。ORF 18在β-和γ-疱疹病毒中是保守的。通过产生MHV-68 ORF 18-null病毒，我们表征了需要ORF 18功能的病毒裂解级联的阶段。基因表达谱和定量的病毒DNA合成的ORF 18无效的病毒显示，早期基因的表达和病毒DNA复制不受影响，但是，后期基因的转录被废除。因此，我们已经确定了一种γ疱疹病毒编码的因子，该因子对于独立于病毒DNA合成的晚期基因的表达至关重要。
Lytic replication of the tumor-associated human gammaherpesviruses Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus has important implications in pathogenesis and tumorigenesis. Herpesvirus lytic genes have been temporally classified as exhibiting immediate-early (IE), early, and late expression kinetics. Though the regulation of IE and early gene expression has been studied extensively, very little is known regarding the regulation of late gene expression. Late genes, which primarily encode virion structural proteins, require viral DNA replication for their expression. We have identified a murine gammaherpesvirus 68 (MRV-68) early lytic gene, ORF18, essential for viral replication. ORF18 is conserved in both beta- and gammaherpesviruses. By generating an MHV-68 ORF18-null virus, we characterized the stage of the virus lytic cascade that requires the function of ORF18. Gene expression profiling and quantitation of viral DNA synthesis of the ORF18-null virus revealed that the expression of early genes and viral DNA replication were not affected; however, the transcription of late genes was abolished. Hence, we have identified a gammaherpesvirus-encoded factor essential for the expression of late genes independently of viral DNA synthesis.