Division of Viral Products, OVRR, CBER, Food and Drug Administration , Silver Spring, Maryland 20993, United States.
Division of Biotechnology Research and Review II, CDER, Food and Drug Administration , Silver Spring, Maryland 20993, United States.
J Proteome Res. 2017 Sep 1;16(9):3287-3297. doi: 10.1021/acs.jproteome.7b00286. Epub 2017 Aug 16.
Susceptibility to influenza A virus is determined by a balance of viral and host factors. The genetic background of the host contributes to the severity of disease, but the influenza-related proteomes of cells from different individuals have not been compared. We used high-resolution mass spectrometry to identify proteins in normal human bronchial epithelial (NHBE) cells isolated from three different donors. Infection of each NHBE cell culture with influenza A/California/07/2009 (H1N1) resulted in expression of viral proteins and a variety of host proteins, including interferons, interferon-stimulated genes, and secreted chemokines/cytokines. The expression level of viral proteins corresponded to the level of host proteins that support influenza infection (i.e., pro-viral proteins); however, production of infectious virus was inversely related to the levels of antiviral proteins, suggesting that a balance of pro-viral proteins and the antiviral response controls virus replication. In summary, our results demonstrate that expression levels of pro-viral as well as antiviral factors are different for each donor and suggest that relative quantitation of these factors may provide a way to identify individuals or population groups who are susceptible to severe influenza disease.
宿主对甲型流感病毒的易感性是由病毒和宿主因素共同决定的。宿主的遗传背景会影响疾病的严重程度，但尚未比较过来自不同个体的细胞与流感相关的蛋白质组。我们使用高分辨率质谱法鉴定了从三位不同供体分离的正常人类支气管上皮 (NHBE) 细胞中的蛋白质。将甲型流感 A/加利福尼亚/07/2009（H1N1）分别感染每个 NHBE 细胞培养物，导致病毒蛋白和多种宿主蛋白的表达，包括干扰素、干扰素刺激基因和分泌趋化因子/细胞因子。病毒蛋白的表达水平与支持流感感染的宿主蛋白（即促病毒蛋白）的水平相对应；然而，感染性病毒的产生与抗病毒蛋白的水平呈负相关，这表明促病毒蛋白和抗病毒反应的平衡控制着病毒复制。总之，我们的研究结果表明，每个供体的促病毒和抗病毒因子的表达水平不同，并表明这些因子的相对定量可能为鉴定易患严重流感疾病的个体或人群提供一种方法。
