GSE122031
Single-cell transcriptome of human epithelial cells reveals novel insights into early innate immune responses to influenza virus and viral antagonism
Despite intense study, the complexity of interactions between viral and host cell mechanisms have ensured that the cellular innate immune response to influenza infection is still not well understood, especially at early time points following infection. Single cell RNA sequencing provides a new approach with which we can not only examine these early time points of cellular response, but also examine the heterogeneity of that response and more intensely examine patterns of expression that are hidden from bulk sample sequencing. As part of a larger study investigating the immune response of lung epithelial cells to influenza infection, we performed single-cell RNA expression profiling on A549 cells, a lung epithelial cell line, undergoing either a mock infection or infection by the influenza strain PR8-NS1-GFP at MOIs of 2.0 and 0.2. We measured single cell RNA expression at 4 hours and 12 hours post infection. We found a MOI-dependent negative correlation between expression of viral genes and cellular genes, suggesting an antagonist effect of the viral proteins in the innate immune response at the transcriptional level. Also, we found an unexpected early induction of some interferon inducible genes at higher levels in infected than bystander cells, consistent with autocrine activation. Finally, IFN lambda 1 showed broad expression among infected and bystander cells, indicating a possible paracrine component to induction.hile the cellular innate immune response to influenza infection has been studied intensely, there are still many unanswered questions, especially relating to the early Overall design: Single cell RNA sequencing was conducted on six samples of the human epithelial cell line A549. Samples were either MOCK infected or infected by influenza viral strain PR8-NS1-GFP at MOI of 2.0 or 0.2 and measured at 4 or 12 hours post infection..