The cellular Activating Protein 1 cFos regulates Influenza A virus replication: raw data

Previous research has demonstrated that Influenza A virus (IAV) infection activates AP-1 transcription factors as part of the antiviral response. In this study, we identified cFos as the most upregulated AP-1 transcription factor during IAV infection in A549 human lung cells. Surprisingly, the knockdown of cFos resulted in impaired IAV replication. Fluorescence microscopy and functional analyses indicated that cFos is implicated in IAV infection through its nuclear function, rather than its cytoplasmic role as an activator of lipid synthesis. The investigation into the role of cFos in IAV infection revealed increased apoptosis and elevated interferon-β mRNA levels in cFos knockdown A549 cells during IAV infection. This suggests that cFos may enhance cell survival and reduce interferon-β expression during infection, thereby facilitating IAV proliferation. Furthermore, the levels of viral NA mRNA and the expression of late viral proteins NA and M2 decreased upon cFos knockdown. Overall, this study identifies cFos as a proviral factor for IAV, through the modulation of innate immunity and apoptosis during infection, and potentially by supporting the viral transcription.

既往研究已证实，甲型流感病毒（Influenza A virus, IAV）感染可激活AP-1转录因子（AP-1 transcription factors），作为抗病毒应答的核心组分。本研究中，我们在感染IAV的A549人肺细胞中鉴定出cFos为上调幅度最高的AP-1转录因子。令人意外的是，敲低cFos会导致IAV复制能力受损。荧光显微镜（Fluorescence microscopy）观察与功能分析（functional analyses）结果显示，cFos通过其核功能而非作为脂质合成（lipid synthesis）激活因子的胞质功能参与IAV感染过程。对cFos在IAV感染中作用的探究发现，IAV感染期间，cFos敲低的A549细胞中细胞凋亡（apoptosis）水平升高、干扰素-β mRNA（interferon-β mRNA）含量显著增加。这表明cFos可在感染进程中增强细胞存活并降低干扰素-β的表达，进而促进IAV增殖。此外，敲低cFos后，病毒NA mRNA水平以及晚期病毒蛋白NA与M2的表达均出现显著下调。综上，本研究确认cFos是IAV的促病毒因子（proviral factor），其作用机制可能为在感染过程中调控固有免疫（innate immunity）与细胞凋亡，并可能辅助病毒转录。