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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先天的防御肽BPIFA1/SPLUNC1限制了流感病毒感染。
DOI：
10.1038/mi.2017.109
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发表时间：
2018-05
影响因子：
8
通讯作者：
Stewart JP
中科院分区：
文献类型：
--
作者：
Akram KM;Moyo NA;Leeming GH;Bingle L;Jasim S;Hussain S;Schorlemmer A;Kipar A;Digard P;Tripp RA;Shohet RV;Bingle CD;Stewart JP
气道上皮分泌的蛋白质在先天防御感染中起作用。杀菌/增加通透性的含折叠家族成员A1 （BPIFA1）分泌到气道中，在细菌感染时具有保护作用，但是否也具有抗病毒作用尚不清楚。为了确定BPIFA1在宿主防御甲型流感病毒（IAV）感染中的作用，并找到潜在的防御机制，我们开发了缺乏BPIFA1的转基因小鼠模型，并将这些模型与体外三维小鼠气管上皮细胞（mTEC）培养物结合使用，研究其抗病毒特性。我们发现BPIFA1在抵抗IAV感染的粘膜防御中具有重要作用。IAV感染后BPIFA1分泌高度调节。缺乏BPIFA1的小鼠在感染后体重下降更多，支持更高的病毒载量，病毒更早到达外周肺，表明感染控制存在缺陷。mTEC培养的进一步分析表明，bpifa1缺陷细胞结合了更多的病毒颗粒，显示出IAV核糖核蛋白复合物的核输入增加，并支持更高水平的病毒复制。我们的研究结果确定了BPIFA1在感染的初始阶段通过抑制IAV的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 mTEC 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.
影响因子：
8
作者：
Akram, K. M.;Moyo, N. A.;Stewart, J. P.
通讯作者：
Stewart, J. P.