Response of primary human airway epithelial cells to influenza infection: a quantitative proteomic study.

Response of primary human airway epithelial cells to influenza infection: a quantitative proteomic study.
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DOI:
10.1021/pr300239r
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发表时间:
2012-08-03
影响因子:
4.4
通讯作者:
Coombs KM
Coombs KM
中科院分区:
生物学2区
文献类型:
--
作者:
Kroeker AL;Ezzati P;Halayko AJ;Coombs KM

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甲型流感病毒在年度流行和全球大流行期间都会造成很大的健康负担。然而,由于病毒进化迅速,设计有效的疫苗和治疗方案已被证明是困难的。因此,识别与病毒感染和复制相关的宿主蛋白以建立潜在的新的抗病毒靶点可能是有益的。我们之前已经在连续培养的A549细胞中检测了感染小鼠适应病毒株A/PR/8/34(H1N1;PR8)的宿主蛋白反应。我们在这里识别和测量在更相关的原代人支气管呼吸道上皮(HBAE)细胞中差异调节的宿主蛋白。2DLC-MS/MS共鉴定出3740个胞浆HBAE蛋白,其中52个蛋白在感染Pr8后≥表达上调2倍,41个蛋白≥表达下调2倍。上调的HBAE蛋白主要聚集在干扰素信号、其他宿主防御过程和分子运输中,而下调的蛋白与细胞死亡信号通路、细胞黏附和运动以及脂质代谢相关。与感染流感的A549细胞相比,表明流感诱导的宿主细胞发生了一些常见的变化,包括防御反应、分子运输蛋白和细胞黏附。然而,HBAE特异性改变包括干扰素和细胞死亡信号。这些数据指出了流感在连续和原代细胞系和/或肺泡和支气管上皮细胞中复制之间的重要差异。
Influenza A virus exerts a large health burden during both yearly epidemics and global pandemics. However, designing effective vaccine and treatment options has proven difficult since the virus evolves rapidly. Therefore, it may be beneficial to identify host proteins associated with viral infection and replication to establish potential new antiviral targets. We have previously measured host protein responses in continuously cultured A549 cells infected with mouse-adapted virus strain A/PR/8/34(H1N1; PR8). We here identify and measure host proteins differentially regulated in more relevant primary human bronchial airway epithelial (HBAE) cells. A total of 3740 cytosolic HBAE proteins were identified by 2D LC–MS/MS, of which 52 were up-regulated ≥2-fold and 41 were down-regulated ≥2-fold after PR8 infection. Up-regulated HBAE proteins clustered primarily into interferon signaling, other host defense processes, and molecular transport, whereas down-regulated proteins were associated with cell death signaling pathways, cell adhesion and motility, and lipid metabolism. Comparison to influenza-infected A549 cells indicated some common influenza-induced host cell alterations, including defense response, molecular transport proteins, and cell adhesion. However, HBAE-specific alterations consisted of interferon and cell death signaling. These data point to important differences between influenza replication in continuous and primary cell lines and/or alveolar and bronchial epithelial cells.
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