对A型流感病毒的蛋白质组和遗传分析确定了泛病毒宿主目标
Kelsey M Haas1,2,3,4, Michael J McGregor1,2,3,4, Mehdi Bouhaddou1,2,3,4
1J. David Gladstone Institutes, San Francisco, CA, 94158, USA.
Nature communications
|September 27, 2023
概括
这项研究确定了流感A病毒 (IAV) 复制必需的宿主蛋白质,揭示了AHNAK和COPB1作为广泛抗流感和冠状病毒治疗的点.
科学领域:
- 病毒学 病毒学
- 宿主-病原体相互作用
- 药物发现 药物发现 药物发现
背景情况:
- 流感A型病毒 (IAV) 构成了严重的公共卫生威胁,抗病毒选择有限.
- 确定宿主导疗法 (HDT) 对于开发新的抗病毒策略至关重要.
研究的目的:
- 为了全面地绘制宿主-IAV蛋白质-蛋白质相互作用,并确定宿主因子对于IAV感染至关重要.
- 发现流感和其他呼吸道病毒的潜在泛病毒治疗点.
主要方法:
- 在多个IAV菌株和人类细胞类型中进行亲和净化-质谱和全球蛋白/蛋白质丰度分析.
- 严重流感患者的整体外基因组测序,以确定相关的宿主遗传因素.
- siRNA敲击屏幕,以评估宿主因素对IAV复制的影响.
主要成果:
- 确定了332个IAV-人体蛋白-蛋白相互作用和13个IAV调节的激酶.
- 确定AHNAK和COPB1是IAV和SARS-CoV-2感染的重要宿主因素.
- 针对已识别的宿主因子的16种化合物抑制了IAV复制,其中2种具有泛抗病毒活性.
结论:
- 建立了人类细胞中IAV感染的综合网络模型.
- 艾哈纳克和COPB1是开发新型泛病毒宿主导疗法的有希望的目标.
- 针对CDK2和FLT3等宿主因子,为广泛的抗病毒治疗提供了一个潜在的战略.
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