The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus.

The IFITM proteins mediate cellular resistance to influenza A H1N1 virus, West Nile virus, and dengue virus.
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DOI:
10.1016/j.cell.2009.12.017
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发表时间:
2009-12-24
期刊:
影响因子:
64.5
通讯作者:
Elledge SJ
Elledge SJ
中科院分区:
生物学1区
文献类型:
--
作者:
Brass AL;Huang IC;Benita Y;John SP;Krishnan MN;Feeley EM;Ryan BJ;Weyer JL;van der Weyden L;Fikrig E;Adams DJ;Xavier RJ;Farzan M;Elledge SJ

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流感病毒利用宿主细胞机制进行复制,导致呼吸道疾病的流行。反过来,宿主表达抗病毒限制因子以防御感染。为了找到甲型H1N1流感病毒感染的宿主细胞修饰剂,我们使用功能基因组筛选并鉴定了超过120种甲型流感病毒依赖因子,这些因子在内体酸化、囊泡运输、线粒体代谢和RNA剪接中发挥作用。我们发现干扰素诱导的跨膜蛋白IFITM 1、2和3限制了甲型流感病毒复制的早期步骤。IFITM蛋白赋予对甲型流感病毒的基本抗性,但也可被I型和II型干扰素诱导,并且对于干扰素的病毒抑制作用至关重要。进一步的表征表明,IFITM蛋白抑制黄病毒的早期复制,包括登革热病毒和西尼罗河病毒。总的来说,这项工作确定了一个新的抗病毒限制因子家族,介导细胞对至少三种主要人类病原体的抗性。
Influenza viruses exploit host cell machinery to replicate, resulting in epidemics of respiratory illness. In turn, the host expresses anti-viral restriction factors to defend against infection. To find host-cell modifiers of influenza A H1N1 viral infection, we used a functional genomic screen and identified over 120 influenza A virus-dependency factors with roles in endosomal acidification, vesicular trafficking, mitochondrial metabolism and RNA splicing. We discovered that the interferon-inducible trans-membrane proteins, IFITM1, 2 and 3, restrict an early step in influenza A viral replication. The IFITM proteins confer basal resistance to influenza A virus, but are also inducible by interferons type I and II, and are critical for interferon's virustatic actions. Further characterization revealed that the IFITM proteins inhibit the early replication of flaviviruses, including dengue virus and West Nile virus. Collectively this work identifies a new family of anti-viral restriction factors that mediate cellular resistance to at least three major human pathogens.
跨膜蛋白的脆弱性干扰素诱导基因家族与小鼠的生殖细胞规范有关。
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