An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection
An innate defense peptide BPIFA1/SPLUNC1 restricts influenza A virus infection
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DOI：
10.1038/mi.2017.45
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发表时间：
2018-01-01
影响因子：
8
通讯作者：
Stewart, J. P.
中科院分区：
文献类型：
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作者：
Akram, K. M.;Moyo, N. A.;Stewart, J. P.
呼吸道上皮细胞分泌的蛋白质在抵抗感染的先天防御中发挥作用。含杀菌/通透性增加倍数的家族成员A1（BPIFA 1）分泌到气道中，在细菌感染期间具有保护作用，但尚不清楚它是否也具有抗病毒作用。为了确定宿主防御甲型流感病毒（IAV）感染的作用，并找到潜在的防御机制，我们开发了BPIFA 1缺陷的转基因小鼠模型，并将其与体外三维小鼠气管上皮细胞（mTEC）培养物结合使用，以研究其抗病毒特性。我们发现BPIFA 1在粘膜防御IAV感染中具有重要作用。IAV感染后BPIFA 1分泌高度调节。缺乏BPIFA 1的小鼠在感染后体重减轻更多，支持更高的病毒载量，并且病毒更早到达外周肺，这表明感染控制存在缺陷。进一步的分析表明，使用m TEC文化BPIFA 1缺陷的细胞结合更多的病毒颗粒，显示增加IAV核糖核蛋白复合物的核输入，并支持更高水平的病毒复制。我们的研究结果确定了BPIFA 1在感染的初始阶段通过抑制IAV结合和进入气道上皮细胞的关键作用。
The airway epithelium secretes proteins that function in innate defense against infection. Bactericidal/permeability-increasing fold-containing family member A1 (BPIFA1) is secreted into airways and has a protective role during bacterial infections, but it is not known whether it also has an antiviral role. To determine a role in host defense against influenza A virus (IAV) infection and to find the underlying defense mechanism, we developed transgenic mouse models that are deficient in BPIFA1 and used these, in combination with in vitro three-dimensional mouse tracheal epithelial cell (mTEC) cultures, to investigate its antiviral properties. We show that BPIFA1 has a significant role in mucosal defense against IAV infection. BPIFA1 secretion was highly modulated after IAV infection. Mice deficient in BPIFA1 lost more weight after infection, supported a higher viral load and virus reached the peripheral lung earlier, indicative of a defect in the control of infection. Further analysis using m TEC cultures showed that BPIFA1-deficient cells bound more virus particles, displayed increased nuclear import of IAV ribonucleoprotein complexes, and supported higher levels of viral replication. Our results identify a critical role of BPIFA1 in the initial phase of infection by inhibiting the binding and entry of IAV into airway epithelial cells.