向宿主转录因子HSF1可以防止人细胞巨乳病毒在体外和体内生殖的复制
bioRxiv : the preprint server for biology
|October 10, 2024
概括
人类细胞巨乳病毒 (HCMV) 感染激活了热冲击转录因子1 (HSF1). 用SISU-102抑制HSF1可减少病毒复制,为HCMV提供潜在的宿主导抗病毒疗法.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 目前FDA批准的抗病毒药物对抗人类细胞巨乳病毒 (HCMV) 有局限性,包括向晚期病毒复制阶段,副作用和耐药性.
- 针对HCMV感染期间激活的宿主因子是一个有希望的替代策略.
研究的目的:
- 研究热冲击转录因子1 (HSF1) 在HCMV复制中的作用.
- 评估HSF1抑制作为一种潜在的宿主导抗病毒疗法来对抗HCMV.
主要方法:
- 研究了HCMV感染纤维细胞中的HSF1激活和核转位.
- 利用药理抑制 (SISU-102) 和 HSF1.1 的遗传衰竭.
- 评估病毒基因表达和后代的产生.
- 使用人类皮肤异种移植的小鼠模型来评估体内疗效.
主要成果:
- HCMV感染迅速激活HSF1,在病毒复制过程中促进其核转移.
- 抑制HSF1 (预防性或治疗性) 显著减弱病毒基因表达,包括直接早期的基因,并减少病毒的产生.
- 用HSF1抑制剂SISU-102治疗减少了人体皮肤异种移植和传播中的病毒复制.
结论:
- 冠状病毒感染劫持宿主HSF1路径以促进病毒复制.
- HSF1是一种关键的宿主因子,支持HCMV复制周期的多个阶段.
- 向HSF1代表了一种可行的宿主导的抗病毒策略来对抗HCMV.
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