Tonic ISG expression promotes efficient induction of IFNL in response to influenza infection. Tonic ISG expression promotes efficient induction of IFNL in response to influenza infection

The innate immune response, especially the interferon (IFN) response, plays a critical role in limiting initial dissemination of viruses from the site of infection. While the pathogen-associated molecular patterns (PAMPs) and pattern recognition receptors (PRRs) involved in sensing and inducing the innate immune response during influenza A virus (IAV) infections are well-characterized, the factors that regulate IFNL production in infected cells remain poorly understood. Previous studies have highlighted that most infected cells fail to express either type I or III IFNs in response to stimulus, suggesting a regulatory mechanism that controls the activation of IFNs during infection. To investigate the factors influencing IFNL induction during IAV infection, we performed single-cell RNA sequencing (scRNA-seq) of A549 cells infected with A/Perth/16/2009 and sampled at multiple time points post-infection. Using a novel pseudotime analysis approach tailored for temporal scRNA-seq data, we aim to identify host genes whose tonic expression modulates IFNL production in response to IAV infection. Overall design: Comparison of host gene expression in Perth09 (H3N2) infected human alveolar epithelial cells at different times post-infection