Transposable elements are associated with the variable response to influenza infection

• DOI: 10.1101/2022.05.10.491101
• Publication Date: 2022-05-20T11:56:21Z
• Authors: Xun Chen; Alain Sarabia Pacis; Katherine A Aracena; Saideep Gona; Tony Kwan; Cristian Groza; Yen Lung Lin; Renata Helena Mon...; Vania Yotova; Albena Pramatarova; Marie-Michelle Simon; Tomi M. Pastinen; Luis Barreiro; Guillaume Bourque
• Keywords: 0301 basic medicine; 03 medical and health sciences; variable response; epigenetics; influenza infection; transposable elements; Kruppel-associated box zinc finger proteins (KRAB-ZNFs); gene regulation; Article; 3. Good health

SUMMARYInfluenza 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.