Differential Transcriptional Responses in Corneal and Lung Epithelial Cells to Seasonal Influenza with Potential Function of LGALS9

Seasonal flu, primarily caused by influenza A H1N1 and H3N2 subtype viruses or influenza B viruses, is the most prevalent respiratory tract infection globally and leads to substantial morbidity and mortality annually. Despite the influenza virus being initially recognized as a respiratory pathogen with well-characterized transmission through respiratory droplets, its impact on the ocular epithelium and associated gene expression remains relatively unexplored. In this study, we investigated the transcriptional profiles of immortalized human corneal epithelial cells (HCE-S) and A549 human lung epithelial cells infected with H1N1 and H3N2 influenza virus. In comparison with A549 cells, a reduced number of differentially expressed genes was observed in HCE-S upon influenza virus infection. Specifically, there was a significant upregulation of the genes IFI44L and OAS1, along with lower release of the CCL5/RANTES protein. Notably, our findings revealed uniquely upregulated LGALS9 (encoding galectin-9) in HCE-S following infection with the 2009 pandemic H1N1 virus. Furthermore, targeted knockdown of LGALS9 in these cells resulted in a measurable decrease in viral infection, highlighting its role in the cellular responses to influenza virus and suggesting a novel avenue for antiviral therapy. Overall, our findings provide insight into the distinct mechanisms of influenza virus interactions with different epithelial cells and underscore the importance of studying the ocular surface in understanding influenza pathogenesis.