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Critical Care
Published in: Critical Care 1/2020

01-12-2020 | Septic Shock | Research

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

Authors: Marine Mommert, Olivier Tabone, Audrey Guichard, Guy Oriol, Elisabeth Cerrato, Mélanie Denizot, Valérie Cheynet, Alexandre Pachot, Alain Lepape, Guillaume Monneret, Fabienne Venet, Karen Brengel-Pesce, Julien Textoris, François Mallet, MIPrea Study Group, REALISM Study Group

Published in: Critical Care | Issue 1/2020

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Abstract

Background

Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. Numerous studies have explored the complex and dynamic transcriptome modulations observed in sepsis patients, but a large fraction of the transcriptome remains unexplored. This fraction could provide information to better understand sepsis pathophysiology. Multiple levels of interaction between human endogenous retroviruses (HERV) and the immune response have led us to hypothesize that sepsis is associated with HERV transcription and that HERVs may contribute to a signature among septic patients allowing stratification and personalized management.

Methods

We used a high-density microarray and RT-qPCR to evaluate the HERV and Mammalian Apparent Long Terminal Repeat retrotransposons (MaLR) transcriptome in a pilot study that included 20 selected septic shock patients, stratified on mHLA-DR expression, with samples collected on day 1 and day 3 after inclusion. We validated the results in an unselected, independent cohort that included 100 septic shock patients on day 3 after inclusion. We compared septic shock patients, according to their immune status, to describe the transcriptional HERV/MaLR and conventional gene expression. For differential expression analyses, moderated t tests were performed and Wilcoxon signed-rank tests were used to analyze RT-qPCR results.

Results

We showed that 6.9% of the HERV/MaLR repertoire was transcribed in the whole blood, and septic shock was associated with an early modulation of a few thousand of these loci, in comparison to healthy volunteers. We provided evidence that a subset of HERV/MaLR and conventional genes were differentially expressed in septic shock patients, according to their immune status, using monocyte HLA-DR (mHLA-DR) expression as a proxy. A group of 193 differentially expressed HERV/MaLR probesets, tested in an independent septic shock cohort, identified two groups of patients with different immune status and severity features.

Conclusion

We demonstrated that a large, unexplored part of our genome, which codes for HERV/MaLR, may be linked to the host immune response. The identified set of HERV/MaLR probesets should be evaluated on a large scale to assess the relevance of these loci in the stratification of septic shock patients. This may help to address the heterogeneity of these patients.
Appendix
Available only for authorised users
Footnotes
1
Repertoire: within HERV-V3 microarray, the probesets are grouped into four repertoire: (1) genes, (2) HERV prototype (good annotation), (3) HERV/MaLR Dfam (lower quality annotation), and (4) other probesets (such as lncRNA)
 
2
Class: each HERV group belongs to different classes: class I (Gamma- and Epsilon-like), II (Beta-like), and III (Spuma-like), according to their pol region and phylogeny similarity
 
3
Group: also improperly named as “families.” HERV loci belongs to HERV groups based on sequence (nucleotide and Pol amino acid), similarity, degree of fit, and taxonomic markers
 
4
LTR: repeat flanking sequence of HERV that allows the regulation of their expression may have a promoter or polyadenylation signal function
 
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Metadata
Title
Dynamic LTR retrotransposon transcriptome landscape in septic shock patients
Authors
Marine Mommert
Olivier Tabone
Audrey Guichard
Guy Oriol
Elisabeth Cerrato
Mélanie Denizot
Valérie Cheynet
Alexandre Pachot
Alain Lepape
Guillaume Monneret
Fabienne Venet
Karen Brengel-Pesce
Julien Textoris
François Mallet
MIPrea Study Group
REALISM Study Group
Publication date
01-12-2020
Publisher
BioMed Central
Keyword
Septic Shock
Published in
Critical Care / Issue 1/2020
Electronic ISSN: 1364-8535
DOI
https://doi.org/10.1186/s13054-020-2788-8

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