在缺少关键病毒转活剂的情况下,Sp1促进了持续的HSV-1基因表达
Catherine N Sodroski1,2, Hyung Suk Oh1, Shu-Fan Chou1
1Department of Microbiology, Blavatnik Institute, Harvard Medical School, Boston, Massachusetts, USA.
mBio
|February 13, 2024
概括
细胞转录因子Sp1支持单纯疹病毒1 (HSV-1) 复制和基因表达,特别是当病毒激活剂有限或受到免疫压力时. 这突显了Sp1在HSV-1在具有挑战性的细胞环境中的生存中的作用.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 细胞生物学 细胞生物学
背景情况:
- 简单疹病毒 (HSV) 的复制取决于涉及病毒和细胞因素的转录级联.
- 一个无处不在的细胞转录因子Sp1与HSV-1基因的促进体结合,但其在病毒复制中的确切作用尚未完全理解.
- 了解Sp1的贡献对于破译HSV-1的生命周期和持续性至关重要.
研究的目的:
- 为了研究Sp1在HSV-1流性基因级联中的特定作用.
- 为了确定Sp1是否支持HSV-1转录和复制在有限的病毒转活器条件下.
- 探索Sp1对病毒免疫逃避和潜伏的潜在贡献.
主要方法:
- 在人类前皮纤维细胞中减少Sp1,以评估其对HSV-1感染的影响.
- 感染野生型 (WT) HSV-1,VP16缺陷和ICP0缺陷病毒.
- 干扰素治疗纤维细胞以模拟免疫压力.
- 在分化感官神经元中分析Sp1和Sp1家族转录因子表达.
主要成果:
- 当病毒转活剂 (VP16或ICP0) 缺乏时,Sp1显著增加了HSV-1转录水平,蛋白质表达和复制.
- 在干扰素治疗后,Sp1增强了WT HSV-1的转录和复制,这表明它在免疫逃避中发挥了作用.
- 在分化神经元中减少Sp1表达表明在HSV-1延迟中发挥了潜在作用.
结论:
- 在维持HSV-1基因表达和复制方面,Sp1起着至关重要的作用,特别是在诸如有限的病毒激活剂或免疫挑战等不利条件下.
- 在HSV-1促进体中存在Sp1结合位可能是一种病毒策略,以确保在各种宿主细胞类型和条件中实现基因表达和复制.
- 在这些条件下Sp1的功能可能有助于HSV-1建立和维持感染的能力.
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