microRNA-mediated GALNT3 upregulation facilitates mucin production and viral replication in influenza A virus-infected respiratory epithelial cells

Viral infections affecting the upper or lower respiratory tract induce mucin production in the epithelial surfaces of the respiratory cells. However, a little is known about how mucins are produced on the surfaces of respiratory epithelial cells and affects viral replication. In the course of the investigation of the cellular responses in the early stage of Influenza A virus (IAV) infection, we found that two miRNAs, miR-221 and miR-17-3p, which target the mRNA of GalNAc transferase 3 (GALNT3), are rapidly down-regulated as early as 1.5 h post-infection. To understand the early host cell responses to the IAV infection, we performed miRNA microarray analysis using a human alveolar adenocarcinoma cell line, A549 cells, infected with influenza A/Puerto Rico/8/34 H1N1 (PR8) virus. We isolated the cellular RNAs at 0.5, 1.5 and 4.5 h post-infection and detected significant changes in the global profile of miRNA expression after infection with IAV. mouse embryonic fibroblasts. Each sample was run in duplicate.

侵袭上、下呼吸道的病毒感染，可诱导呼吸道上皮细胞表面的黏蛋白生成。然而，目前学界对呼吸道上皮细胞表面黏蛋白的生成机制及其对病毒复制的调控作用仍知之甚少。在探究甲型流感病毒（Influenza A virus, IAV）感染早期的细胞应答过程中，我们发现两种靶向N-乙酰半乳糖胺转移酶3（GalNAc transferase 3, GALNT3）信使RNA（mRNA）的微小RNA（microRNA, miRNA）——miR-221与miR-17-3p，可在感染后1.5小时即快速下调。为阐明宿主细胞针对甲型流感病毒感染的早期应答机制，本研究采用感染了甲型流感病毒A/Puerto Rico/8/34 H1N1（PR8株）的人肺泡腺癌细胞系A549细胞，开展微小RNA芯片分析（miRNA microarray analysis）。我们于感染后0.5、1.5及4.5小时分离细胞总RNA，并检测到甲型流感病毒感染后细胞内微小RNA表达的全局谱发生显著变化。小鼠胚胎成纤维细胞。每个样本均设置双份重复检测。