Zhu Fan, Liu Yi, Lei Jiehao, Li Xinxing, Jiang Zexu, Dong Xuan, Gu Ying, Li Young
BGI Research, Hangzhou, China.
College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
Nat Commun. 2025 Aug 14;16(1):7534. doi: 10.1038/s41467-025-62779-7.
Human endogenous retroviruses constitute a significant portion of the human genome and play complex roles in gene regulation and disease processes. However, the expression pattern and disease associations of specific retroviral loci remain pooly understood. This study examines the expression and regulatory mechanisms of these retroviral elements in immune cells. Utilizing single-cell RNA sequencing data from peripheral blood mononuclear cells, we identify 41,460 expressed retroviral loci, with 1936 showing cell type-specific expression. We further detect 3463 conditionally independent expression quantitative trait loci linked to retroviral elements, highlighting their potential role in mediating genetic variants and disease associations. Notably, these retroviral sequences associate significantly with autoimmune diseases, with specific loci demonstrating pleiotropic associations with disease-related genes. Our findings suggest that these elements are not merely genomic remnants but active participants in cellular regulation and disease progression. This work advances understanding of human-retroviral coevolution and highlights potential therapeutic targets in immune disorders.
人类内源性逆转录病毒构成了人类基因组的重要部分，并在基因调控和疾病进程中发挥着复杂的作用。然而，特定逆转录病毒基因座的表达模式和与疾病的关联仍知之甚少。本研究考察了这些逆转录病毒元件在免疫细胞中的表达及调控机制。利用外周血单个核细胞的单细胞RNA测序数据，我们鉴定出41460个表达的逆转录病毒基因座，其中1936个表现出细胞类型特异性表达。我们进一步检测到3463个与逆转录病毒元件相关的条件独立表达数量性状基因座，突出了它们在介导基因变异和疾病关联中的潜在作用。值得注意的是，这些逆转录病毒序列与自身免疫性疾病显著相关，特定基因座显示出与疾病相关基因的多效性关联。我们的研究结果表明，这些元件不仅是基因组残余物，而且是细胞调控和疾病进展的积极参与者。这项工作推进了对人类与逆转录病毒共同进化的理解，并突出了免疫紊乱中潜在的治疗靶点。
