Abstract
BackgroundHuman 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.ResultsWe 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.ConclusionThis 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.
Highlights
Human Endogenous Retroviruses (HERVs) and Mammalian apparent Long Terminal Repeats (LTR)-retrotransposons (MaLRs) represent the 8% of our genome and are distributed among our 46 chromosomes
We investigated HERVs and Mammalian apparent LTR-retrotransposons (MaLR) expression in Peripheral blood mononuclear cell (PBMC) by modelling monocyte endotoxin tolerance, consisting in low-dose LPS priming of PBMCs and mimicking monocyte anergy observed in sepsis patients [50,51,52]
In addition to the gene probesets designed in U133plus2 and HTA Affymetrix formats, the chip contains a set of highly informative probesets corresponding to accurately annotated HERV loci hereinafter referred to as “HERV_prototypes”, and two sets of probesets corresponding to roughly annotated HERVs/MaLRs elements called hereafter “HERV_Dfam” and “MaLR_Dfam”
Summary
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. Retrovirus-like sequences represent the 8% of the human genome [1] They consist of some 200,000 Human Endogenous Retroviruses (HERVs) and 240,000 Mammalian Apparent LTR retrotransposons (MaLRs). MaLR structure is similar except for the absence of an env gene. Based on the homology of pol sequences between HERVs and exogenous retroviruses, these well-defined groups can be classified as gamma-, beta-, spuma- and epsilon- retroviruses [10]
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