Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

Area of Science:

• Genomics
• Immunology
• Retrovirology

Background:

• Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection.
• A significant portion of the human transcriptome, including human endogenous retroviruses (HERVs), remains unexplored in sepsis.
• HERVs interact with the immune system, suggesting a potential role in sepsis pathophysiology and patient stratification.

Purpose of the Study:

• To investigate the transcription of HERVs and Mammalian Apparent Long Terminal Repeat retrotransposons (MaLRs) in sepsis patients.
• To determine if HERV/MaLR transcription patterns can differentiate sepsis patient subgroups.
• To explore the potential of HERVs/MaLRs in personalized sepsis management.

Main Methods:

• High-density microarray and RT-qPCR were used to analyze HERV/MaLR and conventional gene expression in septic shock patients.
• Samples were collected from 20 patients (pilot study) and 100 patients (validation cohort) at different time points.
• Differential gene expression analysis was performed, comparing septic patients with healthy volunteers and stratifying patients based on immune status (mHLA-DR expression).

Main Results:

• Approximately 6.9% of the HERV/MaLR repertoire was transcribed in whole blood, with early modulation observed in sepsis patients compared to healthy controls.
• A subset of HERV/MaLR and conventional genes showed differential expression based on immune status (mHLA-DR proxy).
• A panel of 193 differentially expressed HERV/MaLR probesets identified two patient groups with distinct immune status and severity features in an independent cohort.

Conclusions:

• A significant, unexplored portion of the genome encoding HERVs/MaLRs is linked to the host immune response in sepsis.
• The identified HERV/MaLR probesets warrant large-scale evaluation for their relevance in stratifying septic shock patients.
• These findings may contribute to addressing the heterogeneity observed in sepsis patients and enabling personalized treatment strategies.