增殖细胞核抗原抑制剂阻断了单纯疹病毒感染的不同阶段
Jessica E Packard1, Maya R Williams1, Daniel P Fromuth1
1Department of Biological Sciences, Duquesne University, Pittsburgh, Pennsylvania, United States of America.
PLoS pathogens
|July 24, 2023
概括
细胞PCNA抑制剂通过防止必要的病毒和细胞蛋白与病毒DNA结合,抑制DNA合成和病毒产生来阻止单纯疹病毒1型 (HSV-1) 复制.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物化学 生化学
背景情况:
- 增殖细胞核抗原 (PCNA) 对于细胞DNA复制和修复至关重要,作为蛋白质招募的支架.
- PCNA对于简单疹病毒1型 (HSV-1) 感染至关重要,与病毒复制分叉相关,尽管HSV-1编码了自己的聚合酶过程性因子 (UL42).
研究的目的:
- 阐明PCNA在HSV-1DNA复制和感染中的作用.
- 研究两种不同的PCNA抑制剂PCNA-I1和T2AA对HSV-1传染周期和病毒DNA的蛋白质招募的影响.
主要方法:
- 用PCNA抑制剂PCNA-I1和T2AA治疗HSV-1感染细胞.
- 评估病毒DNA复制,晚期基因表达和病毒产生.
- 利用新生DNA (aniPOND) 上蛋白质的加速原生分离来分析蛋白质-DNA相互作用.
主要成果:
- PCNA-I1治疗减少了HSV-1DNA复制,晚期基因表达和病毒产生.
- T2AA治疗减少了晚期病毒基因表达和传染性病毒的产生.
- T2AA抑制了病毒 uracil glycosylase (UL2) 和转录因子到病毒 DNA 的招募,影响基切割修复.
- PCNA-I1降低了病毒DNA聚合酶 (UL30) 和PCNA相互作用蛋白与病毒DNA的关联.
结论:
- 针对细胞PCNA的抑制剂通过阻止病毒DNA中关键病毒和细胞因子的招募来破坏HSV-1感染周期.
- 这些抑制剂有效地抑制病毒DNA合成和合过程,为病毒复制机制和潜在的治疗标提供了洞察力.
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