Division of Biotechnology Review and Research II, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Division of Biotechnology Review and Research II, Center for Drug Evaluation and Research, Food and Drug Administration, Silver Spring, MD, USA.
Virus Res. 2019 Apr 15;264:1-7. doi: 10.1016/j.virusres.2019.02.002. Epub 2019 Feb 16.
Influenza is an acute respiratory disease that can cause local annual epidemics and worldwide pandemics of different morbidity and mortality. Our understanding of host factors that modulate the frequency and severity of influenza virus infections is less than complete. In this study, we examined the inter-individual variations in the innate immune responses to H1N1 and H3N2 influenza A viruses (IAV) using primary cultures of normal human bronchial epithelial (NHBE) cells derived from two different donors (D1 and D2). Although IAV replication kinetics were similar in cultures derived from these two donors, the levels of type III interferons (IFNs) were significantly higher in D1 cells compared to D2 cells (˜31-fold↑ in D1 cells versus D2 cells; P < 0.05). The levels of IFN-λ1 protein at individual time points as well as the total amounts of IFN-λ1 secreted over 72 h were also significantly higher in D1 than in D2 NHBE cells (0.7-7.7-fold↑, P < 0.05). The relative levels of IFN-stimulated gene (ISG) expression also differed significantly between D1 and D2 cells. Our data indicate that donor-specific differences can result in significant differences in IFN and ISG induction by human airway epithelium.
流感是一种急性呼吸道疾病，可导致局部年度流行和全球不同发病率和死亡率的大流行。我们对调节流感病毒感染频率和严重程度的宿主因素的了解还不完整。在这项研究中，我们使用源自两个不同供体（D1 和 D2）的正常人支气管上皮（NHBE）细胞的原代培养物，研究了对 H1N1 和 H3N2 甲型流感病毒（IAV）的固有免疫反应的个体间差异。尽管来自这两个供体的培养物中的 IAV 复制动力学相似，但 D1 细胞中的 III 型干扰素（IFN）水平明显高于 D2 细胞（D1 细胞中约为 31 倍↑，D2 细胞；P <0.05）。在 D1 细胞中，IFN-λ1 蛋白的水平在各个时间点以及在 72 小时内分泌的 IFN-λ1 总量也明显高于 D2 NHBE 细胞（0.7-7.7 倍↑，P <0.05）。IFN 刺激基因（ISG）表达的相对水平在 D1 和 D2 细胞之间也有显著差异。我们的数据表明，供体特异性差异可导致人呼吸道上皮细胞中 IFN 和 ISG 诱导的显着差异。
