Dissection of influenza infection in vivo by single-cell RNA-sequencing. Dissection of influenza infection in vivo by single-cell RNA-sequencing

The influenza virus is a major cause of morbidity and mortality worldwide, yet, the impact of intracellular viral invasion and the cellular response diversity remain uncharacterized. By massively parallel single-cell RNA-seq we comprehensively mapped the host lung response to in-vivo influenza infection in wild-type and Irf7-knockout mice across nine immune and non-immune cell types. We found an unexpected high prevalence of infected cells in all cell types, showed that infection is a characteristic property of cell types that is independent of type-I interferon activity, and demonstrated that all cell types responded primarily with a robust generic transcriptional response. Analysis of the viral and host transcriptomes in the same single cell enabled us to resolve the heterogeneity of bystander (exposed but uninfected) as compared to viral-infected cells. Our results highlight novel markers specific for influenza-infected as opposed to bystander cells, opening new avenues for targeted therapy aimed exclusively at infected cells. Overall design: We used Massively parallel single-cell RNA-seq (MARS-seq) to characterize single cell RNA-seq of immune (CD45+) and non-immune (CD45-) cells derived from the lungs of influenza-treated and PBS-treated mice.