Table_1_Transcriptome Profiling Reveals Differential Effect of Interleukin-17A Upon Influenza Virus Infection in Human Cells.docx

Influenza A virus (IAV) has developed elegant strategies to utilize cellular proteins and pathways to promote replication and evade the host antiviral response. Identification of these sabotaged host factors could increase the number of potential antiviral drug targets. Here, IAV A/PR/8/34 (PR8)- and A/California/04/2009-infected A549 and 293T cells displayed differential virus replication. To determine the host cellular responses of A549 and 293T cells to IAV infection, RNA-seq was used to identify differentially expressed genes. Our data revealed that IAV-infected A549 cells activated stronger virus-sensing signals and highly expressed cytokines, which play significant roles in initiating the innate immune and inflammatory responses. In addition, IAV-infected 293T cells displayed weak immune signaling and cytokine production. Remarkably, IL-17A and associated genes were highly enriched in IAV-infected 293T cells. Furthermore, IL-17A can partially facilitate A549 cell infection by the PR8 strain and PR8-infected IL-17A knock-out mice consistently exhibited decreased weight loss and reduced lung immunopathology, as compared to controls. This work uncovered the differential responses of cells infected with two H1N1 IAV strains and the potential roles of IL-17A in modulating virus infection.

流感病毒A型（IAV）巧妙地利用细胞蛋白和通路促进复制并规避宿主抗病毒反应。识别这些被破坏的宿主因子可增加潜在抗病毒药物靶点的数量。在本研究中，感染了IAV A/PR/8/34（PR8）和A/加利福尼亚/04/2009的A549和293T细胞显示出不同的病毒复制特征。为了确定A549和293T细胞对IAV感染的宿主细胞反应，我们使用了RNA测序技术来识别差异表达的基因。我们的数据揭示了感染IAV的A549细胞激活了更强的病毒感知信号并高度表达细胞因子，这些因子在启动先天免疫和炎症反应中发挥着重要作用。此外，感染IAV的293T细胞表现出较弱的免疫信号和细胞因子产生。值得注意的是，IL-17A及其相关基因在感染IAV的293T细胞中高度富集。此外，IL-17A可以部分促进PR8菌株对A549细胞的感染，与对照相比，PR8感染IL-17A敲除小鼠表现出体重减轻减少和肺免疫病理学降低。本研究揭示了两种H1N1 IAV菌株感染细胞的差异性反应，以及IL-17A在调节病毒感染中的潜在作用。