Transposable elements are associated with the variable response to influenza infection

SUMMARY Influenza A virus (IAV) infections are frequent every year and result in a range of disease severity. Given that transposable elements (TEs) contribute to the activation of innate immunity, we wanted to explore their potential role in this variability. Transcriptome profiling in monocyte-derived macrophages from 39 individuals following IAV infection revealed significant inter-individual variation in viral load post-infection. Using ATAC-seq we identified a set of TE families with either enhanced or reduced accessibility upon infection. Of the enhanced families, 15 showed high variability between individuals and had distinct epigenetic profiles. Motif analysis showed an association with known immune regulators in stably enriched TE families and with other factors in variable families, including KRAB-ZNFs. We also observed a strong association between basal TE transcripts and viral load post infection. Finally, we built a predictive model suggesting that TEs, and host factors regulating TEs, contribute to the variable response to infection.