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向宿主转录因子HSF1可以防止人细胞巨乳病毒在体外和体外复制

Dilruba Akter¹, Juthi Biswas¹, Shima Moradpour¹

¹Department of Microbiology & Immunology, SUNY Upstate Medical University, Syracuse, NY, 13210, USA.

Antiviral research

|March 27, 2025

概括

人类细胞巨乳病毒 (HCMV) 感染激活热冲击转录因子1 (HSF1),这是一个关键的宿主因子. 用SISU-102抑制HSF1提供了一个有前途的宿主导抗病毒策略来阻止HCMV复制.

科学领域:

病毒学病毒学
分子生物学分子生物学
免疫学免疫学免疫学

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,包括针对晚期复制阶段,副作用和耐药性.
针对对病毒复制至关重要的宿主因素,提出了一个替代策略,以克服现有的抗HCMV药物限制.

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作为潜在的宿主导抗病毒向对HCMV的目标.

主要方法:

在纤维细胞中对HCMV感染时评估HSF1激活和核转位.
利用药理抑制 (SISU-102) 和 HSF1.1 的遗传衰竭.
研究了HSF1抑制对病毒基因表达和后代产生的影响.
采用人类皮肤异种移植的小鼠模型来评估SISU-102.2的体内疗效.

主要成果:

HCMV感染迅速激活HSF1,导致其核重新定位,在复制过程中持续.
预防性或治疗性抑制HSF1显著减少病毒基因表达 (包括直接早期基因) 和病毒产生.
SISU-102治疗减弱了人类皮肤异种移植中的HCMV复制,并减少了体内病毒传播.

结论:

冠状病毒感染劫持宿主HSF1路径以促进病毒复制.
HSF1是一个关键的宿主因子,调节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.

关键词:

细胞巨乳病毒病毒.热冲击因子 1 的热冲击因子 1 .宿主指导的抗病毒药物压力反应应对压力.病毒复制是病毒的复制.

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