Endogenous Retroviruses Transcriptional Modulation After Severe Infection, Trauma and Burn.

Olivier Tabone,Fabienne Venet,Camille Jourdan,Alexandre Pachot,Julien Textoris,Elisabeth Cerrato,Bernard Allaouchiche,François Mallet,Alain Lepape,Guillaume Monneret,Marine Mommert,Thomas Rimmelé,Matthieu Legrand

doi:10.3389/fimmu.2018.03091

Abstract

Although human endogenous retroviruses (HERVs) expression is a growing subject of interest, no study focused before on specific endogenous retroviruses loci activation in severely injured patients. Yet, HERV reactivation is observed in immunity compromised settings like some cancers and auto-immune diseases. Our objective was to assess the transcriptional modulation of HERVs in burn, trauma and septic shock patients. We analyzed HERV transcriptome with microarray data from whole blood samples of a burn cohort (n = 30), a trauma cohort (n = 105) and 2 septic shock cohorts (n = 28, n = 51), and healthy volunteers (HV, n = 60). We described expression of the 337 probesets targeting HERV from U133 plus 2.0 microarray in each dataset and then we compared HERVs transcriptional modulation of patients compared to healthy volunteers. Although all 4 cohorts contained critically ill patients, the majority of the 337 HERVs was not expressed (around 74% in mean). Each cohort had differentially expressed probesets in patients compared to HV (from 19 to 46). Strikingly, 5 HERVs were in common in all types of severely injured patients, with 4 being up-modulated in patients. We highlighted co-expressed profiles between HERV and nearby CD55 and CD300LF genes as well as autonomous HERV expression. We suggest an inflammatory-specific HERV transcriptional response, and importantly, we introduce that the HERVs close to immunity-related genes might have a role on its expression.

Highlights

Human Endogenous Retroviruses (HERVs) are former exogenous retroviruses which have infected germinal cells and became integrated in our genome million years ago [1]
We studied the in vivo modulation of the Human endogenous retrovirus (HERV) transcriptome in three clinical relevant models of acute inflammatory injury: a burn, a trauma and 2 septic shock cohorts
We took advantage of previous microarray analyses on four cohorts of severely injured patients to assess the modulation of HERV transcriptome in acute inflammation

Summary

Introduction

Human Endogenous Retroviruses (HERVs) are former exogenous retroviruses which have infected germinal cells and became integrated in our genome million years ago [1]. These rare events happened several times in evolution. Most of HERVs in our genome are solo LTRs [1] resulting from recombination between 5′ and 3′ proviral LTRs. LTRs are critical elements that control viral gene expression either as promoters, enhancers or as polyadenylation signals. Within or downstream of a “conventional” protein coding gene, LTRs can modulate its expression pattern [2, 3]. Very few is known about of the transcriptional modulation of such elements in pathological contexts but in cancers [like testicular cancer [7] or colorectal cancer [8]] and auto-immune diseases [like multiple sclerosis [9,10,11]]

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