Interferon-Induced Transmembrane Protein-Mediated Inhibition of Host Cell Entry of Ebolaviruses.
Interferon-Induced Transmembrane Protein-Mediated Inhibition of Host Cell Entry of Ebolaviruses.
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DOI：
10.1093/infdis/jiv255
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发表时间：
2015-10-01
期刊：
影响因子：
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通讯作者：
Pöhlmann S
中科院分区：
文献类型：
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作者：
Wrensch F;Karsten CB;Gnirß K;Hoffmann M;Lu K;Takada A;Winkler M;Simmons G;Pöhlmann S
埃博拉病毒在人类和非人灵长类动物中具有高致病性，对公共卫生构成严重威胁。干扰素诱导的跨膜（IFITM）蛋白可以限制埃博拉病毒、甲型流感病毒和其他包膜病毒的进入。然而，IFITM蛋白的抗病毒活性的广度和机制还不完全清楚。在这里，我们采用埃博拉病毒糖蛋白假型载体和埃博拉病毒样颗粒来解决这个问题。我们表明，IFITM蛋白抑制细胞进入不同的埃博拉病毒，并证明I型干扰素诱导IFITM蛋白表达的巨噬细胞，主要的病毒目标。此外，我们发现IFITM蛋白通过不同的机制阻断甲型流感病毒和埃博拉病毒的进入，并提供了抗体和IFITM蛋白可以协同抑制埃博拉病毒进入细胞的证据。这些结果提供了深入了解IFITM蛋白在埃博拉病毒感染中的作用，并提出了一种机制，通过该机制，抗体虽然在体外中和性差，但可能有助于体内病毒控制。
Ebolaviruses are highly pathogenic in humans and nonhuman primates and pose a severe threat to public health. The interferon-induced transmembrane (IFITM) proteins can restrict entry of ebolaviruses, influenza A viruses, and other enveloped viruses. However, the breadth and mechanism of the antiviral activity of IFITM proteins are incompletely understood. Here, we employed ebolavirus glycoprotein–pseudotyped vectors and ebolavirus-like particles to address this question. We show that IFITM proteins inhibit the cellular entry of diverse ebolaviruses and demonstrate that type I interferon induces IFITM protein expression in macrophages, major viral targets. Moreover, we show that IFITM proteins block entry of influenza A viruses and ebolaviruses by different mechanisms and provide evidence that antibodies and IFITM proteins can synergistically inhibit cellular entry of ebolaviruses. These results provide insights into the role of IFITM proteins in infection by ebolaviruses and suggest a mechanism by which antibodies, though poorly neutralizing in vitro, might contribute to viral control in vivo.