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.