Arumugaswami Vaithilingaraja, Wu Ting-Ting, Martinez-Guzman DeeAnn, Jia Qingmei, Deng Hongyu, Reyes Nichole, Sun Ren
Department of Molecular and Medical Pharmacology, David Geffen School of Medicine, University of California, Los Angeles, 23-120 Center for Health Sciences, Los Angeles, CA 90095-1735, USA.
J Virol. 2006 Oct;80(19):9730-40. doi: 10.1128/JVI.00246-06.
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 (MHV-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.
肿瘤相关的人类γ疱疹病毒——爱泼斯坦-巴尔病毒（EB病毒）和卡波西肉瘤相关疱疹病毒的裂解复制在发病机制和肿瘤发生中具有重要意义。疱疹病毒的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。尽管对IE和早期基因表达的调控已进行了广泛研究，但对于晚期基因表达的调控却知之甚少。主要编码病毒体结构蛋白的晚期基因，其表达需要病毒DNA复制。我们鉴定出一种小鼠γ疱疹病毒68（MHV-68）早期裂解基因ORF18，它对病毒复制至关重要。ORF18在β和γ疱疹病毒中均保守。通过构建一种缺失MHV-68 ORF18的病毒，我们确定了病毒裂解级联反应中需要ORF18功能的阶段。对缺失ORF18病毒的基因表达谱分析和病毒DNA合成定量显示，早期基因的表达和病毒DNA复制未受影响；然而，晚期基因的转录被消除。因此，我们鉴定出一种γ疱疹病毒编码的因子，它对于晚期基因的表达至关重要，且独立于病毒DNA合成。
