Contribution of Syncytins and Other Endogenous Retroviral Envelopes to Human Placenta Pathologies

Bolze, Pierre‐Adrien; Mommert, Marine; Mallet, François

doi:10.1016/bs.pmbts.2016.12.005

Cited by 41 publications

(35 citation statements)

References 196 publications

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“…The immunosuppressive activity is generally assumed to be exerted by a domain in the transmembrane envelope protein which is highly conserved across exogenous and endogenous retroviral envelope sequences [5–8, 30]. The immunosuppressive properties of retroviral envelope are rarely addressed in immunization studies, and there are only few reports showing a dampening effect of envelope on the immune responses to other immunogens [31–34].…”

Section: Discussionmentioning

confidence: 99%

Interference of retroviral envelope with vaccine-induced CD8+ T cell responses is relieved by co-administration of cytokine-encoding vectors

Bongard¹,

Lapuente

Windmann³

et al. 2017

Retrovirology

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BackgroundRetroviral envelope (Env) proteins are known to exhibit immunosuppressive properties, which become apparent not only in retroviral infections, but also in gene-based immunizations using retroviral immunogens, where envelope interferes with the induction of CD8+ T cell responses towards another, simultaneously or subsequently delivered, immunogen.ResultsIn the Friend retrovirus mouse model, immunization with a plasmid encoding the Friend murine leukemia virus (F-MuLV) Leader-Gag protein resulted in induction of a strong GagL85–93-specific CD8+ T cell response, while the response was completely abrogated by co-immunization with an F-MuLV Env-encoding plasmid. In order to overcome this interference of retroviral envelope, we employed plasmids encoding the cytokines interleukin (IL) 1β, IL2, IL12, IL15, IL21, IL28A or granulocyte–macrophage colony-stimulating factor (GM-CSF) as genetic adjuvants. Co-application of plasmids encoding IL2, IL12, IL21, IL28A and especially GM-CSF rescued the induction of GagL85–93-specific CD8+ T cells in mice vaccinated with FV Leader-Gag and Env. Mice that were immunized with plasmids encoding Leader-Gag and Env and the cytokines IL1β, IL12, IL15, IL28A or GM-CSF, but not Leader-Gag and Env without any cytokine, showed significantly reduced viral loads upon a high-dose Friend virus challenge infection.ConclusionsOur data demonstrate the potency of cytokine-encoding vectors as adjuvants and immune modulators in composite vaccines for anti-retroviral immunization.Electronic supplementary materialThe online version of this article (doi:10.1186/s12977-017-0352-7) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Interference of retroviral envelope with vaccine-induced CD8+ T cell responses is relieved by co-administration of cytokine-encoding vectors

Bongard¹,

Lapuente

Windmann³

et al. 2017

Retrovirology

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“…The differences observed between whole blood and PBMCs may be due to (i) the variability among whole blood samples, (ii) the cell type composition, such as the presence of neutrophils in the whole blood, and (iii) the stimuli released from the endothelial environment. We observed a high proportion of gamma-retroviruses, which included HERV families that potentially code for envelope proteins that comprise an immunosuppressive domain (ISD) [44]. These families included HERV-H, HERV-W, HERV-FRD, HERV-Fc2, and HERV-T [45].…”

Section: Discussionmentioning

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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“…CD274 or programmed death‐ligand 1 (PD‐L1) is an immune checkpoint molecule that may have a role in immune suppression during pregnancy . Syncytin‐1 mediates trophoblast fusion and may have a role in tolerance to fetal antigens . Herein, CD200 was the most widely expressed marker and syncytin‐1 the least expressed.…”

Section: Discussionmentioning

confidence: 99%

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors

Fitzgerald

Gomez‐Lopez

Erez

et al. 2018

American J Rep Immunol

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A system of ex vivo placental villous and amnion tissues can be used as an adequate model to study placenta metabolic activity in normal and complicated pregnancies, in particular to characterize EVs by their surface markers and by encapsulated proteins. Establishment and benchmarking the placenta ex vivo system may provide new insight in the functional status of this organ in various placental disorders, particularly regarding the release of EVs and cytokines. Such EVs may have a prognostic value for pregnancy complications.

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Contribution of Syncytins and Other Endogenous Retroviral Envelopes to Human Placenta Pathologies

Cited by 41 publications

References 196 publications

Interference of retroviral envelope with vaccine-induced CD8+ T cell responses is relieved by co-administration of cytokine-encoding vectors

Interference of retroviral envelope with vaccine-induced CD8+ T cell responses is relieved by co-administration of cytokine-encoding vectors

Dynamic LTR retrotransposon transcriptome landscape in septic shock patients

Extracellular vesicles generated by placental tissues ex vivo: A transport system for immune mediators and growth factors

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