Deng Hongyu, Young Arthur, Sun Ren
Department of Molecular & Medical Pharmacology, UCLA AIDS Institute, Jonsson Comprehensive Cancer Center, and the Molecular Biology Institute, University of California at Los Angeles, Los Angeles, CA 90095, USA1.
J Gen Virol. 2000 Dec;81(Pt 12):3043-3048. doi: 10.1099/0022-1317-81-12-3043.
Rta, mainly encoded by open reading frame 50 (ORF50), is the product of an immediate-early gene of human herpesvirus-8 (HHV-8)/Kaposi's sarcoma-associated herpesvirus. Rta is a transcriptional activator that is both necessary and sufficient to disrupt viral latency and activate the expression of downstream viral lytic genes. We report that ectopically expressed Rta protein could also activate the rta promoter on a reporter plasmid up to 144-fold, both in latently infected B cells and in uninfected epithelial cells, and that this activation was dose-dependent. Furthermore, by analysing the 5' untranslated region using ribonuclease protection assays, we demonstrated that transfection of an Rta expression plasmid into latently infected cells activated the expression of rta transcripts from endogenous viral genomes. We propose that auto-activation of the immediate-early gene, rta, is an important strategy for HHV-8 to effectively respond to environmental stimuli and maximally activate the virus lytic cycle.
Rta主要由开放阅读框50(ORF50)编码,是人类疱疹病毒8型(HHV - 8)/卡波西肉瘤相关疱疹病毒即刻早期基因的产物。Rta是一种转录激活因子,对于破坏病毒潜伏状态并激活下游病毒裂解基因的表达而言,它既是必需的也是充分的。我们报告称,异位表达的Rta蛋白在潜伏感染的B细胞和未感染的上皮细胞中,均可将报告质粒上的rta启动子激活至144倍,且这种激活呈剂量依赖性。此外,通过使用核糖核酸酶保护分析来分析5'非翻译区,我们证明将Rta表达质粒转染到潜伏感染的细胞中可激活内源性病毒基因组中rta转录本的表达。我们提出,即刻早期基因rta的自激活是HHV - 8有效响应环境刺激并最大程度激活病毒裂解周期的重要策略。