Human endogenous retroviruses in the aetiology of MS

Christensen, Tove

doi:10.1111/ane.12836

Cited by 17 publications

(14 citation statements)

References 33 publications

(10 reference statements)

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“…Particularly in MS, it is conceivable that the formation of HERV Env proteins trigger a damaging cascade that eventually leads to the symptoms of the disease. This assumption could help to integrate unexpected findings, such as pre-active plaques, into the sequence of pathological events (Christensen, 2017 ). A deeper understanding of HERV expression under physiological and pathophysiological conditions and their interaction with the immune system might help to better explain and combine several factors that contribute to MS.…”

Section: Discussionmentioning

confidence: 99%

Human Endogenous Retroviruses and Their Putative Role in the Development of Autoimmune Disorders Such as Multiple Sclerosis

Gröger

Cynis

2018

Front. Microbiol.

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Human endogenous retroviruses (HERVs) are remnants of retroviral germ line infections of human ancestors and make up ~8% of the human genome. Under physiological conditions, these elements are frequently inactive or non-functional due to deactivating mutations and epigenetic control. However, they can be reactivated under certain pathological conditions and produce viral transcripts and proteins. Several disorders, like multiple sclerosis or amyotrophic lateral sclerosis are associated with increased HERV expression. Although their detailed contribution to individual diseases has yet to be elucidated, an increasing number of studies in vitro and in vivo suggest HERVs as potent modulators of the immune system. They are able to affect the transcription of other immune-related genes, interact with pattern recognition receptors, and influence the positive and negative selection of developing thymocytes. Interestingly, HERV envelope proteins can both stimulate and suppress immune responses based on different mechanisms. In the light of HERV proteins becoming an emerging drug target for autoimmune-related disorders and cancer, we will provide an overview on recent findings of the complex interactions between HERVs and the human immune system with a focus on autoimmunity.

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Section: Discussionmentioning

confidence: 99%

Human Endogenous Retroviruses and Their Putative Role in the Development of Autoimmune Disorders Such as Multiple Sclerosis

Gröger

Cynis

2018

Front. Microbiol.

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“…Multiple sclerosis (MS) is the most common immune-mediated disease of the central nervous system [1]. The etiology of MS is unknown; a combination of several factors may be involved, including genetics, environment, and possibly viruses including human endogenous retroviruses (HERVs) [2,3]. Several studies demonstrated that MS lesions contain multiple leukocytes, including adaptive and innate immune cells, all of which are believed to contribute to lesion formation and disease progression [4,5].…”

Section: Accepted Manuscript Introductionmentioning

confidence: 99%

Immunomodulating peptides derived from different human endogenous retroviruses (HERVs) show dissimilar impact on pathogenesis of a multiple sclerosis animal disease model

Bahrami

Gryz

Graversen

et al. 2018

Clinical Immunology

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Retroviruses including Human Endogenous Retroviruses (HERVs), contain a conserved region with highly immunomodulatory functions in the transmembrane proteins in envelope gene (env) named immunosuppressive domain (ISU). In this report, we demonstrate that Env59-GP3 peptide holds therapeutic potential in a mouse model of myelin oligodendrocyte glycoprotein (MOG)-induced experimental autoimmune encephalomyelitis (EAE). The results show that this specific HERV-H derived ISU peptide, but not peptide derived from another env gene HERV-K, decreased the development of EAE in C57BL/6 mice, accompanied by reduced demyelination and inhibition of inflammatory cells. Moreover, here we tested the effect of peptides on macrophages differentiation. The treatment with Env59-GPS peptide modulate the pro-inflammatory M1 profile and anti-inflammatory M2 macrophages, being shown by inhibiting inflammatory M1 hallmark genes/cytokines expression and enhancing expression of M2 associated markers. These results demonstrate that Env59-GP3 ISU peptide has therapeutic potential in EAE possibly through inducing the polarization of M2 macrophages and inhibiting inflammatory responses.

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“…This protein has critical roles in many diseases. 12,[31][32][33][34][35][36][37][38][39][40] However, the exact regulatory mechanism of syncytin-1 in EC is poorly understood. To solve this problem, we transfected the expression of syncytin-1 in EC cells by pc-Syncytin-1 and shSyncytin-1 and analyzed the effect of the abnormal expression of syncytin-1 on cell proliferation and cell metastasis.…”

Section: Discussionmentioning

confidence: 99%

Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma

Liu

Wen

et al. 2018

OTT

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Background: Endometrial carcinoma (EC) is the most common and lethal malignancy worldwide. Syncytin-1 is expressed in multiple types of cancer. However, the expression pattern and potential mechanism of syncytin-1 and its clinical significance in EC remain unclear. Materials and methods: We analyzed 130 primary EC specimens from Binzhou Medical University to investigate the clinical role of syncytin-1 in EC by using different advanced pathological stages of EC tissues. Kaplan-Meier analysis was used to measure the overall survival of EC patients. Syncytin-1 expression was analyzed by Western blot assays in HECCL-1 and RL-95-2 cells. Cell proliferation, cycle, migration, and invasion abilities were detected by cell counting kit-8, flow cytometry, and transwell assays. AKT and epithelial-mesenchymal transition (EMT)-related genes were assessed by Western blot assays in HECCL-1 and RL-95-2 cells. Results: Syncytin-1 was upregulated in EC tissues and cells and was related to clinical stages, expression of ER, Ki-67, and overall survival of EC. Functional research revealed that overexpression of syncytin-1 can promote cell proliferation, cell cycle progression, and the migration and invasion of EC cells. Suppression of syncytin-1 expression also inhibited cell proliferation and apoptosis in vitro. The expression of syncytin-1 substantially improved the expression levels of EMT-related genes (vimentin, E-cadherin, slug, and ZEB1) but significantly decreased those of epithelial markers (N-cadherin and snail). In addition, we found that syncytin-1 was not correlated with AKT-related genes (total-AKT, p-AKT, and vinculin). Conclusion: Our results suggested that syncytin-1 may promote aggressive behavior and can serve as a novel prognostic biomarker for EC. Our study provides new insights into the regulatory mechanism of EMT signaling.

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Human endogenous retroviruses in the aetiology of MS

Cited by 17 publications

References 33 publications

Human Endogenous Retroviruses and Their Putative Role in the Development of Autoimmune Disorders Such as Multiple Sclerosis

Human Endogenous Retroviruses and Their Putative Role in the Development of Autoimmune Disorders Such as Multiple Sclerosis

Immunomodulating peptides derived from different human endogenous retroviruses (HERVs) show dissimilar impact on pathogenesis of a multiple sclerosis animal disease model

Upregulation of syncytin-1 promotes invasion and metastasis by activating epithelial-mesenchymal transition-related pathway in endometrial carcinoma

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