Transposable elements are associated with the variable response to influenza infection

Xun Chen; Alain Pacis; Katherine A Aracena; Saideep Gona; Tony Kwan; Cristian Groza; Yen Lung Lin; Renata Sindeaux; Vania Yotova; Albena Pramatarova; Marie-Michelle Simon; Tomi Pastinen; Luis B Barreiro; Guillaume Bourque

doi:10.1016/j.xgen.2023.100292

Transposable elements are associated with the variable response to influenza infection

Cell Genom. 2023 Apr 7;3(5):100292. doi: 10.1016/j.xgen.2023.100292. eCollection 2023 May 10.

Authors

Xun Chen¹, Alain Pacis², Katherine A Aracena³, Saideep Gona³, Tony Kwan⁴, Cristian Groza⁵, Yen Lung Lin³, Renata Sindeaux⁶, Vania Yotova⁶, Albena Pramatarova⁴, Marie-Michelle Simon⁴, Tomi Pastinen^{7

8}, Luis B Barreiro^{3

9

10}, Guillaume Bourque^{1

2

4

8}

Affiliations

¹ Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan.
² Canadian Center for Computational Genomics, McGill University, Montréal, QC H3A 0G1, Canada.
³ Department of Human Genetics, University of Chicago, Chicago, IL 60637, USA.
⁴ Victor Phillip Dahdaleh Institute of Genomic Medicine at McGill University, Montréal, QC H3A 0G1, Canada.
⁵ Quantitative Life Science, McGill University, Montréal, QC H3A 1E3, Canada.
⁶ Centre de Recherche, CHU Sainte-Justine, Université de Montréal, Montréal, QC H3T 1C5, Canada.
⁷ Genomic Medicine Center, Children's Mercy Hospital and Research Institute, Kansas City, MO 64108, USA.
⁸ Department of Human Genetics, McGill University, Montreal, QC H3A 0C7, Canada.
⁹ Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.
¹⁰ Committee on Immunology, University of Chicago, Chicago, IL 60637, USA.

Abstract

Influenza A virus (IAV) infections are frequent every year and result in a range of disease severity. Here, we wanted to explore the potential contribution of transposable elements (TEs) to the variable human immune response. Transcriptome profiling in monocyte-derived macrophages from 39 individuals following IAV infection revealed significant inter-individual variation in viral load post-infection. Using transposase-accessible chromatin using sequencing (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 (e.g., BATFs, FOSs/JUNs, IRFs, STATs, NFkBs, NFYs, and RELs) in stably enriched families and with other factors in variable families, including KRAB-ZNFs. We showed that TEs and host factors regulating TEs were predictive of viral load post-infection. Our findings shed light on the role TEs and KRAB-ZNFs may play in inter-individual variation in immunity.

Keywords: Kruppel-associated box zinc finger proteins (KRAB-ZNFs); epigenetics; gene regulation; influenza infection; transposable elements; variable response.