Endogenous Retroviruses Transcriptional Modulation After Severe Infection, Trauma and Burn

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.

Identification of inflammatory subgroups of schizophrenia and bipolar disorder patients with HERV-W ENV antigenemia by unsupervised cluster analysis

“…In view of the findings presented here, it is tempting to speculate that the earlier disease onset in HERV-W ENV pos relative to HERV-W ENV neg BD subjects may involve intricate interactions between the genetic background and exposure to childhood trauma [17]. Based on previous findings showing un-silencing of HERV-W upon infection, inflammation and/or trauma [57][58][59], we speculate that exposure to childhood trauma may be one of events triggering re-activation of HERV-W ENV protein expression, which in turn may maintain inflammatory responses in a chronic state [2,12,[60][61][62][63][64]. The precise mechanisms, by which this reactivation occurs, remain elusive and warrant further investigation.…”

Transcriptome Analyses Implicate Endogenous Retroviruses Involved in the Host Antiviral Immune System through the Interferon Pathway

“…However, it is necessary to explore whether the overall induction of the HERV loci is specific to DENV infection or a common phenomenon associated with viral infections. Although element activation of HERVs after viral infections had been detected using PCR amplification or microarray analysis in some studies (Muradrasoli et al 2006 ; Tabone et al 2018 ), the obtained results may not be comparable with those of other previous studies because the former targeted a limited number of members of the HERV family rather than the overall family. With the rapid development of RNA sequencing technology, RNA-seq datasets have become increasingly popular and are freely shared for scientific research; it is a convenient method for studying genome-wide transcriptional regulation of ERV under a range of physiological or pathological conditions.…”

The Landscape of Featured Metabolism-Related Genes and Imbalanced Immune Cell Subsets in Sepsis

“…To identify differentially expressed genes (DEGs), the microarray data for sepsis were downloaded from the Gene Expression Omnibus (GEO) database ( https://www.ncbi.nlm.nih.gov/geo/ ) under accession numbers GSE95233 ( Tabone et al, 2018 ) and GSE54514 ( Parnell et al, 2013 ). To explore a prognostic gene expression signature for sepsis, dataset GSE95233 was used as the training dataset and then applied to verify the performance of the SVM classifier.…”