Multi-omics data integration reveals the complexity and diversity of host factors associated with influenza virus infection

Influenza viruses pose a significant and ongoing threat to human health. Many host factors have been identified to be associated with influenza virus infection. However, there is currently a lack of an integrated resource for these host factors. This study integrated human genes and proteins associated with influenza virus infections for 14 subtypes of influenza A viruses, as well as influenza B and C viruses, and built a database named H2Flu to store and organize these genes or proteins. The database includes 28,639 differentially expressed genes (DEGs), 1,850 differentially expressed proteins, and 442 proteins with differential posttranslational modifications after influenza virus infection, as well as 3,040 human proteins that interact with influenza virus proteins and 57 human susceptibility genes. Further analysis showed that the dynamic response of human cells to virus infection, cell type and strain specificity contribute significantly to the diversity of DEGs. Additionally, large heterogeneity was also observed in protein-protein interactions between humans and different types or subtypes of influenza viruses. Overall, the study deepens our understanding of the diversity and complexity of interactions between influenza viruses and humans, and provides a valuable resource for further studies on such interactions.