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. Comparison of host gene expression in Perth09 (H3N2) infected human alveolar epithelial cells at different times post-infection

固有免疫应答（innate immune response），尤其是干扰素（interferon, IFN）应答，在限制病毒从感染部位初始播散的过程中发挥关键作用。尽管目前针对甲型流感病毒（influenza A virus, IAV）感染期间参与固有免疫应答感知与诱导的病原体相关分子模式（pathogen-associated molecular patterns, PAMPs）及模式识别受体（pattern recognition receptors, PRRs）已有充分解析，但感染细胞中调控IFNL产生的相关因子仍有待深入阐明。既往研究表明，多数受感染细胞无法在刺激下表达I型或III型干扰素，这提示感染期间存在调控干扰素激活的相关机制。为探究甲型流感病毒感染期间影响IFNL诱导的调控因子，我们对感染A/Perth/16/2009毒株的A549细胞开展了单细胞RNA测序（single-cell RNA sequencing, scRNA-seq），并在感染后多个时间点进行采样。本研究采用针对时序性单细胞RNA测序数据定制优化的新型拟时分析方法，旨在鉴定能够通过稳态表达调控甲型流感病毒感染下IFNL产生的宿主基因。本研究将对感染A/Perth/16/2009（H3N2）的人肺泡上皮细胞在感染后不同时间点的宿主基因表达展开比较分析。