Chen Xun, Pacis Alain, Aracena Katherine A, Gona Saideep, Kwan Tony, Groza Cristian, Lin Yen Lung, Sindeaux Renata, Yotova Vania, Pramatarova Albena, Simon Marie-Michelle, Pastinen Tomi, Barreiro Luis B, Bourque Guillaume
Institute for the Advanced Study of Human Biology (WPI-ASHBi), Kyoto University, Kyoto 606-8501, Japan.
Canadian Center for Computational Genomics, McGill University, Montréal, QC H3A 0G1, Canada.
Cell Genom. 2023 Apr 7;3(5):100292. doi: 10.1016/j.xgen.2023.100292. eCollection 2023 May 10.
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.
甲型流感病毒(IAV)感染每年都很常见,并导致一系列疾病严重程度。在这里,我们想探讨转座元件(TEs)对人类免疫反应变异性的潜在贡献。对39名个体感染IAV后单核细胞来源的巨噬细胞进行转录组分析,发现感染后病毒载量存在显著的个体间差异。使用转座酶可及染色质测序(ATAC-seq),我们鉴定出一组在感染后可及性增强或降低的TE家族。在增强的家族中,有15个在个体间表现出高度变异性,并具有独特的表观遗传特征。基序分析表明,稳定富集家族中与已知免疫调节因子(如BATFs、FOSs/JUNs、IRFs、STATs、NFkBs、NFYs和RELs)有关联,而可变家族中与其他因子有关联,包括KRAB-ZNFs。我们表明,TEs和调节TEs的宿主因子可预测感染后的病毒载量。我们的研究结果揭示了TEs和KRAB-ZNFs在个体间免疫差异中可能发挥的作用。