Ronni T, Matikainen S, Sareneva T, Melén K, Pirhonen J, Keskinen P, Julkunen I
Department of Virology, National Public Health Institute, Helsinki, Finland.
J Immunol. 1997 Mar 1;158(5):2363-74.
The epithelial cells of the respiratory tract are the primary sites of virus replication in influenza A virus infections. We infected human alveolar epithelium-like A549 cells and fibroblast-like human fetal lung (HFL1) cells with a pathogenic influenza A virus (A/Beijing/353/89), and studied the kinetics of infection and the expression of host IFN-alpha/beta, MxA, OAS (2',5'-oligoadenylate synthetase), and HLA class I and II genes. Viral mRNA and protein synthesis was clearly seen in virus-infected lung cells. A549 and HFL1 cells produced only small amounts of IFN-alpha/beta, whereas virus-infected macrophages produced type I IFN very efficiently. The kinetics of IFN-beta gene expression in A549 cells was rapid, as shown by reverse-transcriptase PCR, and IFN-beta mRNA expression levels correlated well to the kinetics of nuclear factor-kappa B transcription factor activation. In influenza A virus-infected A549 and HFL1 cells, MxA gene induction was mediated by IFN-alpha/beta released into the cell culture supernatant, and was prevented by anti-type I IFN Abs. HLA class I Ag expression, which could be activated by IFN in noninfected A549 and HFL1 cells, was not induced in these cells by virus infection. The results suggest that type I IFN are essential for the activation of the antiviral response in lung epithelial cells.
呼吸道上皮细胞是甲型流感病毒感染中病毒复制的主要部位。我们用致病性甲型流感病毒（A/北京/353/89）感染人肺泡上皮样A549细胞和成纤维细胞样人胎儿肺（HFL1）细胞，并研究感染动力学以及宿主干扰素-α/β、Mx蛋白、2',5'-寡腺苷酸合成酶（OAS）以及HLA I类和II类基因的表达。在病毒感染的肺细胞中可清楚地看到病毒mRNA和蛋白质合成。A549和HFL1细胞仅产生少量干扰素-α/β，而病毒感染的巨噬细胞则非常有效地产生I型干扰素。逆转录聚合酶链反应显示，A549细胞中干扰素-β基因表达动力学很快，且干扰素-β mRNA表达水平与核因子-κB转录因子激活动力学密切相关。在甲型流感病毒感染的A549和HFL1细胞中，Mx蛋白基因的诱导是由释放到细胞培养上清液中的干扰素-α/β介导的，且抗I型干扰素抗体可阻止这种诱导。在未感染的A549和HFL1细胞中可被干扰素激活的HLA I类抗原表达，在这些细胞中未被病毒感染诱导。结果表明，I型干扰素对于肺上皮细胞抗病毒反应的激活至关重要。
