Divergent and dynamic activity of endogenous retroviruses in burn patients and their inflammatory potential

Lee, Kang Hoon; Rah, HyungChul; Green, Tajia; Lee, Youngkwan; Lim, Debora; Nemzek, Jean A.; Wahl, Wendy L.; Greenhalgh, David G.; Cho, Ki-Ho

doi:10.1016/j.yexmp.2014.02.001

Cited by 10 publications

(10 citation statements)

References 31 publications

(36 reference statements)

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“…Some authors already focused on HERV detection in blood of burn patients using pan-family RT-PCRs (Y.-J. Lee et al 2013; K.-H. Lee et al 2014). However, very few data are available in human diseases for specific loci.…”

Section: Discussionmentioning

confidence: 99%

“…In vivo, HERVs expression has been detected in the plasma and whole blood samples of burn patients (Y.-J. Lee et al 2013; K.-H. Lee et al 2014) although the studies focused on whole HERVs families, not on specific loci. Studying HERV transcriptome modulation after severe inflammatory injuries could help to better understand pathological states of patients.…”

Section: Introductionmentioning

confidence: 99%

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Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

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Jourdan

et al. 2018

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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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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

Tabone

Mommert

Jourdan

et al. 2018

Preprint

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“…It has been demonstrated that certain TREome genes, such as the envelope genes of MLV-ERVs and MMTV-ERV SAg genes, play functional roles in biological processes (Bentvelzen, 1992; Huber et al, 1994; Kotzin et al, 1993). In addition, TREome (human endogenous retroviruses) gene isoforms isolated from a human burn patient's genomic DNA demonstrated differential potentials for regulating inflammatory mediators, such as IL-6 and IL-1β (Lee et al, 2014). Despite the previous studies which reported a range of functionality of TREome genes in both mice and humans, unfortunately, they are often called non-coding long RNAs in current literature (Geisler and Coller, 2013; Gibb et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Genomic landscapes of endogenous retroviruses unveil intricate genetics of conventional and genetically-engineered laboratory mouse strains

Lee

Lim

Chiu

et al. 2016

Experimental and Molecular Pathology

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Laboratory strains of mice, both conventional and genetically engineered, have been introduced as critical components of a broad range of studies investigating normal and disease biology. Currently, the genetic identity of laboratory mice is primarily confirmed by surveying polymorphisms in selected sets of “conventional” genes and/or microsatellites in the absence of a single completely sequenced mouse genome. First, we examined variations in the genomic landscapes of transposable repetitive elements, named the TREome, in conventional and genetically engineered mouse strains using murine leukemia virus-type endogenous retroviruses (MLV-ERVs) as a probe. A survey of the genomes from 56 conventional strains revealed strain-specific TREome landscapes, and certain families (e.g., C57BL) of strains were discernible with defined patterns. Interestingly, the TREome landscapes of C3H/HeJ (toll-like receptor-4 [TLR4] mutant) inbred mice were different from its control C3H/HeOuJ (TLR4 wild-type) strain. In addition, a CD14 knock-out strain had a distinct TREome landscape compared to its control/backcross C57BL/6J strain. Second, an examination of superantigen (SAg, a “TREome gene”) coding sequences of mouse mammary tumor virus-type ERVs in the genomes of the 46 conventional strains revealed a high diversity, suggesting a potential role of SAgs in strain-specific immune phenotypes. The findings from this study indicate that unexplored and intricate genomic variations exist in laboratory mouse strains, both conventional and genetically engineered. The TREome-based high-resolution genetics surveillance system for laboratory mice would contribute to efficient study design with quality control and accurate data interpretation. This genetics system can be easily adapted to other species ranging from plants to humans.

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“…These retrovirus-like sequences consist of approximately 200,000 human endogenous retroviruses (HERVs) and 240,000 mammalian apparent long terminal repeat retrotransposons (MaLR). The expression of HERVs has been observed in both inflammation [14,15] and immunosuppression [13,16], and the insertional polymorphism of HERV LTRs at the HLA locus has been associated with several auto-immune diseases [17]. In addition, several lines of evidence support the role of HERVs as contributors to the immune response [18].…”

Section: Introductionmentioning

confidence: 99%

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

et al. 2020

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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.

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Divergent and dynamic activity of endogenous retroviruses in burn patients and their inflammatory potential

Cited by 10 publications

References 31 publications

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

Endogenous retroviruses transcriptional modulation after severe infection, trauma and burn

Genomic landscapes of endogenous retroviruses unveil intricate genetics of conventional and genetically-engineered laboratory mouse strains

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

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