Joint research unit, Hospice Civils de Lyon, bioMerieux, Centre Hospitalier Lyon Sud, 165 Chemin du Grand Revoyet, 69310, Pierre-Benite, France.
EA 7426 Pathophysiology of Injury-induced Immunosuppression, University of Lyon1-Hospices Civils de Lyon-bioMérieux, Hôpital Edouard Herriot, 5 Place d'Arsonval, 69437, Lyon, Cedex 3, France.
BMC Genomics. 2018 Jul 5;19(1):522. doi: 10.1186/s12864-018-4901-9.
Human Endogenous Retroviruses (HERVs) and Mammalian apparent LTR-retrotransposons (MaLRs) represent the 8% of our genome and are distributed among our 46 chromosomes. These LTR-retrotransposons are thought to be essentially silent except in cancer, autoimmunity and placental development. Their Long Terminal Repeats (LTRs) constitute putative promoter or polyA regulatory sequences. In this study, we used a recently described high-density microarray which can be used to study HERV/MaLR transcriptome including 353,994 HERV/MaLR loci and 1559 immunity-related genes.
We described, for the first time, the HERV transcriptome in peripheral blood mononuclear cells (PBMCs) using a cellular model mimicking inflammatory response and monocyte anergy observed after septic shock. About 5.6% of the HERV/MaLR repertoire is transcribed in PBMCs. Roughly one-tenth [5.7-13.1%] of LTRs exhibit a putative constitutive promoter or polyA function while one-quarter [19.5-27.6%] may shift from silent to active. Evidence was given that some HERVs/MaLRs and genes may share similar regulation control under lipopolysaccharide (LPS) stimulation conditions. Stimulus-dependent response confirms that HERV expression is tightly regulated in PBMCs. Altogether, these observations make it possible to integrate 62 HERVs/MaLRs and 26 genes in 11 canonical pathways and suggest a link between HERV expression and immune response. The transcriptional modulation of HERVs located close to genes such as OAS2/3 and IFI44/IFI44L or at a great distance from genes was discussed.
This microarray-based approach revealed the expression of about 47,466 distinct HERV loci and identified 951 putative promoter LTRs and 744 putative polyA LTRs in PBMCs. HERV/MaLR expression was shown to be tightly modulated under several stimuli including high-dose and low-dose LPS and Interferon-γ (IFN-γ). HERV incorporation at the crossroads of immune response pathways paves the way for further functional studies and analyses of the HERV transcriptome in altered immune responses in vivo such as in sepsis.
人类内源性逆转录病毒（HERV）和哺乳动物明显的长末端重复逆转录转座子（MaLR）代表了我们基因组的 8%，分布在我们的 46 条染色体中。这些 LTR 逆转录转座子除了在癌症、自身免疫和胎盘发育中，通常被认为是沉默的。它们的长末端重复（LTR）构成了潜在的启动子或聚 A 调节序列。在这项研究中，我们使用了一种最近描述的高密度微阵列，该微阵列可用于研究 HERV/MaLR 转录组，包括 353994 个 HERV/MaLR 基因座和 1559 个免疫相关基因。
我们首次描述了外周血单个核细胞（PBMCs）中 HERV 转录组，使用的细胞模型模拟了败血症休克后观察到的炎症反应和单核细胞无反应性。大约 5.6%的 HERV/MaLR 库在 PBMCs 中转录。大约十分之一[5.7-13.1%]的 LTR 具有潜在的组成型启动子或聚 A 功能，而四分之一[19.5-27.6%]可能从沉默转变为活跃。有证据表明，一些 HERV/MaLR 和基因在脂多糖（LPS）刺激条件下可能具有相似的调控控制。刺激依赖性反应证实，HERV 的表达在 PBMCs 中受到严格调控。总的来说，这些观察结果使得将 62 个 HERV/MaLR 和 26 个基因整合到 11 个经典途径中成为可能，并提示 HERV 表达与免疫反应之间存在联系。讨论了位于 OAS2/3 和 IFI44/IFI44L 等基因附近或远离基因的 HERV 的转录调节。
基于微阵列的方法揭示了 PBMCs 中约 47466 个独特 HERV 基因座的表达，并鉴定了 951 个潜在的启动子 LTR 和 744 个潜在的聚 A LTR。在多种刺激下，包括高剂量和低剂量 LPS 和干扰素-γ（IFN-γ），HERV/MaLR 的表达被证明受到严格调控。HERV 在免疫反应途径的交汇点的整合为进一步的功能研究和分析体内免疫反应改变时 HERV 转录组奠定了基础，例如败血症。
