IFITM3 requires an amphipathic helix for antiviral activity
IFITM3 requires an amphipathic helix for antiviral activity
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DOI：
10.15252/embr.201744100
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发表时间：
2017-10-01
期刊：
影响因子：
7.7
通讯作者：
Yount, Jacob S.
中科院分区：
文献类型：
--
作者：
Chesarino, Nicholas M.;Compton, Alex A.;Yount, Jacob S.
干扰素诱导的跨膜蛋白3（IFITM3）是一种细胞因子，其阻断病毒与细胞膜的融合。IFITM3被认为可以改变膜的曲率和流动性，但其确切的作用机制尚不清楚。使用生物信息学的方法，我们预测IFITM3的二级结构，并确定一个高度保守的，短的两亲性螺旋内的IFITM3以前被认为是一个跨膜结构域的疏水区域。与已知的两亲性螺旋改变膜特性的能力一致，我们表明这种螺旋及其两亲性是流感病毒，寨卡病毒，水泡性口炎病毒，埃博拉病毒和人类免疫缺陷病毒感染的IFITM3依赖性抑制所需的。IFITM 1内的同源两亲性螺旋也是抑制感染所必需的，表明IFITM蛋白具有保守的抗病毒作用机制。我们进一步证明了IFITM3的两亲性螺旋是阻断流感病毒血凝素介导的膜融合所必需的。总的来说，我们的研究结果提供了IFITM蛋白利用两亲性螺旋抑制病毒融合的证据。
Interferon-induced transmembrane protein 3 (IFITM3) is a cellular factor that blocks virus fusion with cell membranes. IFITM3 has been suggested to alter membrane curvature and fluidity, though its exact mechanism of action is unclear. Using a bioinformatic approach, we predict IFITM3 secondary structures and identify a highly conserved, short amphipathic helix within a hydrophobic region of IFITM3 previously thought to be a transmembrane domain. Consistent with the known ability of amphipathic helices to alter membrane properties, we show that this helix and its amphipathicity are required for the IFITM3-dependent inhibition of influenza virus, Zika virus, vesicular stomatitis virus, Ebola virus, and human immunodeficiency virus infections. The homologous amphipathic helix within IFITM1 is also required for the inhibition of infection, indicating that IFITM proteins possess a conserved mechanism of antiviral action. We further demonstrate that the amphipathic helix of IFITM3 is required to block influenza virus hemagglutinin-mediated membrane fusion. Overall, our results provide evidence that IFITM proteins utilize an amphipathic helix for inhibiting virus fusion.