A viral activator of gene expression functions via the ubiquitin-proteasome pathway
A viral activator of gene expression functions via the ubiquitin-proteasome pathway
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DOI：
10.1093/emboj/17.24.7161
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发表时间：
1998-12-15
期刊：
影响因子：
11.4
通讯作者：
Preston, CM
中科院分区：
文献类型：
--
作者：
Everett, RD;Orr, A;Preston, CM
1 型单纯疱疹病毒 (HSV-1) 在感觉神经元中达到潜伏状态并定期重新激活的能力对其生物学和临床特性至关重要。裂解复制过程中整个 152 kb 病毒基因组的活跃转录与潜伏状态形成鲜明对比，潜伏状态的特点是产生一组核保留转录本。因此，潜伏基因组的重新激活以重新启动裂解周期涉及病毒转录活性的深刻变化，但这一基本重要过程发生的机制尚不清楚。在这份报告中，我们表明，泛素-蛋白酶体途径的失活显着抑制了病毒立即早期（IE）蛋白 Vmw110 介导的病毒溶解性感染发作的刺激。类似地，培养细胞中静止病毒基因组的Vmw110依赖性重新激活也依赖于蛋白酶体活性。这些结果首次证明病毒基因组的转录活性可以通过蛋白质稳定性控制途径进行调节。
The ability of herpes simplex virus type 1 (HSV-1) to attain a latent state in sensory neurones and reactivate periodically is crucial for its biological and clinical properties. The active transcription of the entire 152 kb viral genome during lytic replication contrasts with the latent state, which is characterized by the production of a single set of nuclear-retained transcripts, Reactivation of latent genomes to re-initiate the lytic cycle therefore involves a profound change in viral transcriptional activity, but the mechanisms by which this fundamentally important process occurs are yet to be well understood. In this report we show that the stimulation of the onset of viral lytic infection mediated by the viral immediate-early (IE) protein Vmw110 is strikingly inhibited by inactivation of the ubiquitin-proteasome pathway. Similarly, the Vmw110-dependent reactivation of quiescent viral genomes in cultured cells is also dependent on proteasome activity, These results constitute the first demonstration that the transcriptional activity of a viral genome can be regulated by protein stability control pathways.