在缺少ICP2727的简单疹病毒1突变的基因组上异常的RNA聚合酶启动和过程性
Claire H Birkenheuer1, Joel D Baines1
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA.
Journal of virology
|May 23, 2024
概括
简单疹病毒1感染细胞蛋白27 (ICP27) 最初通过抑制RNA聚合酶II (Pol II) 启动和过程性来抑制病毒转录. 后来,ICP27增强了病毒基因上的Pol II过程性.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 基因法规 基因法规
背景情况:
- 简单疹病毒1 (HSV-1) 使用细胞RNA聚合酶II (Pol II) 在感染后不久进行病毒转录.
- 感染细胞蛋白27 (ICP27) 对于处理病毒前mRNA和将病毒mRNA输出到细胞质至关重要.
研究的目的:
- 为了研究ICP27在调节病毒转录和RNA聚合酶II (Pol II) 在HSV-1感染期间使用零突变体的活性中的作用.
- 描述ICP27缺陷对Pol II启动和进程性对病毒基因组在感染后的不同时间点的影响.
主要方法:
- 使用精密核运行,然后进行深度测序 (PRO-seq) 来分析病毒转录.
- 使用PRO-seq数据开发和验证了一个过程性指数,以量化RNA聚合酶II (Pol II) 的过程性.
主要成果:
- ICP27无突变的HSV-1在感染后1.5小时和3小时显示病毒基因组上增加了Pol II和聚氨基化位点的下游积累,表明启动和进程性得到了增强.
- 在6hpi时,特定突变病毒基因上的Pol II积累超过了野生类型病毒的积累,这表明ICP27在早期抑制异常转录中的作用.
- ICP27突变体的PRO-seq配置文件与RNA过程性抑制剂flavopiridol诱导的类似,但不完全相同,这区分了ICP27的作用和病毒DNA复制.
结论:
- ICP27最初通过抑制Pol II启动和降低早期感染阶段 (1.5-3hpi) 的RNA过程性来抑制异常病毒转录.
- ICP27对于在大多数晚期病毒基因上增强6hpi的Pol II过程性至关重要,通过一种与病毒DNA复制中的作用不同的机制.
- 在感染期间,ICP27直接或间接调节特定病毒基因的Pol II活动,包括启动和过程性,在感染期间的确定的时间,超出其在mRNA处理和出口中的已知功能.
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