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.
29 30 number of words: 5504 31 number of figures: 10 32 33 Keywords 34 Endogenous retroviruses -severe inflammatory injuries -septic shock -burn -trauma -transcriptome 35 -host response. 36 37 2 Abstract 38Although human endogenous retroviruses (HERVs) expression is a growing subject of interest, 39 no study focused before on specific endogenous retroviruses loci activation in severely injured 40 patients. Yet, HERV reactivation is observed in immunity compromised settings like some 41 cancers and auto-immune diseases. Our objective was to assess the transcriptional modulation of 42 HERVs in burn, trauma and septic shock patients. We analyzed HERV transcriptome with 43 microarray data from whole blood samples of a burn cohort (n=30), a trauma cohort (n=105) and 44 2 septic shock cohorts (n=28, n=51), and healthy volunteers (HV, n=60). We described 45 expression of the 337 probesets targeting HERV from U133 plus 2.0 microarray in each dataset 46 and then we compared HERVs transcriptional modulation of patients compared to healthy 47 volunteers. Although all 4 cohorts contained very severe patients, the majority of the 337 HERVs 48 was not expressed (around 74% in mean). Each cohort had differentially expressed probesets in 49 patients compared to HV (from 19 to 46). Strikingly, 5 HERVs were in common in all types of 50 severely injured patients, with 4 being up-modulated in patients. We highlighted co-expressed 51 profiles between HERV and nearby gene as well as autonomous HERV expression. We suggest 52 an inflammatory-specific HERV transcriptional response, and importantly, we introduce that the 53 HERVs close to immunity-related genes might have a role on its expression. 54 55 57 infected germinal cells and became integrated in our genome million years ago (Young, Stoye, 58 and Kassiotis 2013). These rare events happened several times in evolution. As retrotransposons, 59
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