ITAF45是皮科纳病毒II型IRES元素的普遍的跨作用因子
Michael A Bellucci1,2, Mehdi Amiri1,2, Stephen Berryman3
1Department of Biochemistry, McGill University, Montreal H3A 1A3, QC, Canada.
概括
细胞蛋白ITAF45对于多种皮科纳病毒的复制至关重要,包括FMDV和EMCV. 通过CRISPR/Cas9淘汰去除它使细胞对这些病毒感染具有抵抗力,突出显示了它作为抗病毒点的潜力.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 生物化学 生物化学
背景情况:
- 皮科纳病毒缺乏5'盖,使用内部核糖体进入点 (IRES) 来进行翻译.
- IRES活动是由被称为IRES转作用因子 (ITAF) 的宿主蛋白调节的.
- 以前,ITAF45被认为是针对口病病毒 (FMDV) 感染的特异性.
研究的目的:
- 调查ITAF45在II型IRES含有皮科纳病毒复制中的更广泛作用.
- 确定ITAF45是否是各种皮科纳病毒的一般宿主因素.
主要方法:
- 在人类细胞系中进行CRISPR/Cas9基因编辑以淘汰ITAF45.
- 感染测定用FMDV,脑肌心炎病毒 (EMCV),泰勒鼠脑炎病毒 (TMEV) 和马鼻炎A病毒 (ERAV).
- 分析ITAF45在提升II型IRES元素的翻译启动方面的作用.
主要成果:
- 在CRISPR/Cas9中,ITAF45的淘汰产生了对口疾病毒,EMCV,TMEV和ERAV感染的抗药性.
- ITAF45被证实是利用II型IRES的皮科纳病毒的普遍宿主因子.
- ITAF45的C端氨酸丰富区域调解病毒RNA结合并增强翻译启动.
结论:
- ITAF45在各种II型IRES皮科纳病毒的复制中发挥着重要的,以前被低估的作用.
- 这些发现挑战了关于ITAF45受限功能的先前假设.
- ITAF45代表了对动物和新兴的人类心脏病毒的有希望的泛病毒治疗标.
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