果RNAi屏幕识别了对流感病毒复制很重要的宿主基因
Linhui Hao1, Akira Sakurai, Tokiko Watanabe
1Institute for Molecular Virology, USA.
Nature
|July 11, 2008
概括
研究人员在Drosophila中使用全基因组RNA干扰 (RNAi) 屏幕来识别对流感病毒复制至关重要的宿主基因. 这种方法加速了新抗病毒药物点的发现,解决了流行性流感准备的紧急需求.
科学领域:
- 病毒学 病毒学
- 遗传学 是一个遗传学.
- 药物发现 药物发现 药物发现
背景情况:
- 病毒依赖宿主细胞机械进行复制.
- 识别宿主因子是抗病毒治疗的关键,但与传统方法具有挑战性.
- 由于疫苗开发障碍和耐药性,A型流感病毒对全球健康构成重大威胁.
研究的目的:
- 建立一个新的全基因组RNA干扰 (RNAi) 查平台,以确定流感病毒复制所必需的宿主基因.
- 在哺乳动物细胞中验证已识别的宿主基因,证明它们与人类流感病毒感染的相关性.
主要方法:
- 在Drosophila melanogaster中进行了全基因组RNAi选,针对13,071个基因.
- 流感病毒被修改为感染和检测Drosophila细胞中的基因表达.
- 测量了记者基因表达,以确定影响病毒复制的基因.
主要成果:
- 鉴定了100多个多索菲拉基因,其抑制影响了流感病毒记者基因表达.
- 三个已识别的多索菲拉基因 (ATP6V0D1,COX6A1,NXF1) 被证实对人类HEK 293细胞中的H5N1和H1N1流感A病毒复制至关重要.
- 查显示了特异性,因为这些基因没有影响囊泡性口腔炎病毒或疫苗病毒复制.
结论:
- 在Drosophila中进行全基因组RNAi查是一种可行且有效的方法,用于发现流感病毒复制所需的新型宿主因素.
- 这种方法可以显著加快对抗病毒药物开发的新目标的识别.
- 这些发现为开发抗流感新型抗病毒疗法提供了基础,这对抗流感的准备工作至关重要.
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