IFITM3限制了与流感相关的发病率和死亡率
Aaron R Everitt1, Simon Clare, Thomas Pertel
1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton CB10 1SA, UK.
Nature
|March 27, 2012
概括
干扰素诱导性跨膜蛋白3 (IFITM3) 对于控制小鼠和人类的流感病毒感染至关重要. 降低IFITM3功能与严重的流感结局有关,强调其在宿主防御中的作用.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 遗传学 遗传学 是一个
背景情况:
- 2009年的H1N1大流行揭示了呼吸道病毒的快速传播和一些人的严重后果.
- 干扰素诱导性跨膜蛋白 (IFITM) 在体外显示出强大的各种病毒的限制,包括流感.
研究的目的:
- 调查IFITM3在宿主防御流感A病毒中的体内作用.
- 为了确定IFITM3遗传变异对人类流感病毒感染严重性的影响.
主要方法:
- 利用一个缺少Ifitm3的淘汰赛小鼠模型来评估流感病毒的挑战性.
- 进行了体外测试,以评估病毒复制和IFITM3功能.
- 在患有H1N1/09.9流感住院患者中,基因型IFITM3等位基因.
主要成果:
- 如果itm3缺乏的小鼠在流感挑战时表现出严重的病毒性肺炎,与野生型小鼠不同.
- 在体外重新引入Ifitm3挽救了病毒限制.
- 在住院患者中,一种特定的小IFITM3基因 (rs12252-C) 被丰富,并且在体外显示出抗病毒活性降低.
结论:
- IFITM3对于体内对流感A病毒的内在免疫力至关重要.
- 在IFITM3的遗传变异显著影响人类流感感染的结果.
- 在调节流感病毒病原性方面,IFITM3充当了关键的单一效应因子.
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