BET抑制剂JQ1减弱了猫白血病病毒DNA,前病毒和抗原在家猫细胞系的生产
Garrick M Moll1, Cheryl L Swenson1,2,3, Vilma Yuzbasiyan-Gurkan1,4,5
1Comparative Medicine & Integrative Biology, College of Veterinary Medicine, Michigan State University, East Lansing, MI 48824, USA.
Viruses
|September 28, 2023
概括
原蛋白和额外终端域 (BET) 蛋白质对于猫类白血病病毒 (FeLV) 复制至关重要. 抑制BET蛋白质显著降低了FeLV负载和前病毒DNA集成,提供了潜在的新治疗策略.
科学领域:
- 病毒学 病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 分子生物学分子生物学
背景情况:
- 猫类白血病病毒 (FeLV) 导致类动物的致命疾病,没有明确的治疗方法.
- 目前针对FeLV的疫苗没有提供灭菌免疫力,因此可能导致持续性感染和病毒储存库.
- 以前已经证明,宿主细胞表观遗传阅读器原体和外终端域 (BET) 蛋白质可以促进小鼠白血病病毒 (MuLV) 复制.
研究的目的:
- 研究BET蛋白在FeLV复制中的作用.
- 确定BET蛋白抑制是否可以降低FeLV病毒载量和集成.
- 探索BET蛋白作为FeLV感染的潜在治疗点.
主要方法:
- 用BET抑制剂 (+) -JQ1.1.治疗猫类细胞系 (81C纤维细胞和3201淋巴瘤细胞)
- 用FeLV.挑战治疗和未治疗的细胞.
- 量化FeLV前病毒载量,总FeLVDNA和p27囊蛋白表达.
- 评估FeLV病毒前期整合水平.
主要成果:
- 用 (+) -JQ1治疗显著降低了FeLV前病毒载量和总FeLVDNA.
- 在接受治疗的细胞中,p27囊蛋白表达显著下降.
- 在BET蛋白抑制后,FeLV前病毒集成在81C和3201细胞系显著减少.
- (+) -JQ1在非致死度下有效.
结论:
- BET蛋白对于有效的FeLV复制,包括前病毒集成至关重要.
- 抑制BET蛋白是一种有前途的治疗策略,用于管理FeLV感染.
- 准宿主细胞表观遗传机器为FeLV.病毒治疗提供了一种新的抗病毒疗法.
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