Document Type

Article

Publication Date

5-10-2023

Identifier

DOI: 10.1016/j.xgen.2023.100292; PMCID: PMC10203045

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.

Journal Title

Cell Genom

Volume

3

Issue

5

First Page

100292

Last Page

100292

Keywords

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

Comments

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Publisher's Link: https://doi.org/10.1016/j.xgen.2023.100292

Download

Share

COinS