Influenza virus has a broad cellular tropism in the respiratory tract. Infected epithelial cells sense the infection and initiate an antiviral response. To define the antiviral response at the earliest stages of infection we used a series of single-cycle reporter viruses. These viral probes demonstrated cells in vivo harbor a range in magnitude of virus replication. Transcriptional profiling of cells supporting different levels of replication revealed tiers of IFN-stimulated gene expression. Uninfected cells and cells with blunted replication expressed a distinct and potentially protective antiviral signature, while cells with high replication expressed a unique reserve set of antiviral genes. Finally, we used these single-cycle reporter viruses to determine the antiviral landscape during virus spread, which unveiled disparate protection of epithelial cell subsets mediated by IFN in vivo. Together these results highlight the complexity of virus–host interactions within the infected lung and suggest that magnitude and round of replication tune the antiviral response.

流感病毒在呼吸道中具有广泛的细胞嗜性。被感染的上皮细胞感觉到感染并开始抗病毒反应。为了确定感染初期的抗病毒反应，我们使用了一系列单周期报告病毒。这些病毒探针证明体内细胞在病毒复制方面具有一定范围。支持不同水平复制的细胞的转录谱分析显示了IFN刺激的基因表达的层次。未感染的细胞和复制能力较弱的细胞表达出独特且具有潜在保护性的抗病毒特征，而复制率高的细胞则表达出独特的储备抗病毒基因。最后，我们使用这些单周期报告病毒来确定病毒传播过程中的抗病毒情况，它揭示了在体内由IFN介导的上皮细胞亚群的完全不同的保护。这些结果加在一起突出了受感染肺内病毒与宿主相互作用的复杂性，并表明复制的数量和轮次可以调节抗病毒反应。