Des séquences rétrovirales endogènes dans le génome humain peuvent jouer un rôle physiologique ou pathologique

Médina, Julie; Charvet, Benjamin; Leblanc, Pascal; Germi, Raphaële; Horvat, Branka; Marche, Patrice N.; Perron, Hervé

doi:10.1051/medsci/20173304009

Cited by 9 publications

(5 citation statements)

References 48 publications

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“…Thus, HERV-W ENV transcription can start from upstream TATA boxes in RBM41 intron 6 ending into its exon 7. The presence of HERV-W U3R regulatory sequences in ERVWE2 locus is allowing interactions with viral encoded or virus-induced molecules as previously reviewed 26 , but may also be involved in a potent (epi)genetic repression of its transcription in about 80% of “non-responding” individuals (versus about 20% of “responders”) 17 .…”

Section: Discussionmentioning

confidence: 98%

An HERV-WENVtranscription in atypical memory B cells linked to COVID-19 evolution and risk for long COVID can express the encoded protein from a ribosome readthrough of mRNA from chromosome X

Brunel,

Paganini,

Galloux

et al. 2024

Preprint

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The human genome comprises 8% of endogenous retroviruses (HERVs). Though HERVS contribute to physiological functions, copies retained pathogenic potential. The HERV-W ENV protein was shown expressed in patients with worse COVID-19 symptoms and post-COVID syndrome. A significant detection of the mRNA encoding HERV-W ENV from patients with COVID-19 in B cells from RNAseq reads obtained from peripheral blond mononuclear cells. This data stratified with increased COVID-19 symptoms or with post-acute sequelae of COVID-19 (long COVID) after 3 months. The HERV-WENV-U3RRNA was confirmed to display the best alignment with chromosome X ERVWE2 locus. However, a stop codon precluding its translation was re-addressed after recent understandings of ribosome readthrough mechanisms. Experimental results evidenced that this HERV gene can effectively express a full-length protein in the presence of molecules allowing translation via a readthrough mechanism at the ribosome level. Results not only confirm HERV-WENVRNA origin in these patients, but show for the first time how a defective HERV copy can be translated into a complete protein when specific factors make it possible at the ribosome level. The present proof of concept now requires further studies to identify the factors involved in this newly understood mechanism, following SARS-CoV-2 exposure.

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Section: Discussionmentioning

confidence: 98%

An HERV-WENVtranscription in atypical memory B cells linked to COVID-19 evolution and risk for long COVID can express the encoded protein from a ribosome readthrough of mRNA from chromosome X

Brunel,

Paganini,

Galloux

et al. 2024

Preprint

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“…In a mouse model of latent HSV-2 infection, it was found that HSV-2-induced spinal cord inflammation, although similar to that of ALS patients, was insufficient to induce the characteristic changes in the pathology of ALS ( Cabrera et al, 2020 ). In addition, it has been reported that HSV-1, EBV, CMV, and HHV-6 can cause motor neuron degeneration by activating endogenous retroviruses, thereby inducing the expression of the envelope glycoprotein HERV-K in ALS ( Medina et al, 2017 ; Mayer et al, 2018 ). However, a subsequent study questioned this view due to their failure to detect highly expressed HERV-K RNA in ALS ( Garson et al, 2019 ).…”

Section: Discussionmentioning

confidence: 99%

Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis

Zheng,

Wang,

Lin

et al. 2023

Front. Neurosci.

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BackgroundThe causal associations between infections with human herpes viruses (HHVs) and amyotrophic lateral sclerosis (ALS) has been disputed. This study investigated the causal associations between herpes simplex virus (HSV), varicella-zoster virus (VZV), Epstein–Barr virus (EBV), cytomegalovirus (CMV), HHV-6, and HHV-7 infections and ALS through a bidirectional Mendelian randomization (MR) method.MethodsThe genome-wide association studies (GWAS) database were analyzed by inverse variance weighted (IVW), MR-Egger, weighted median, simple mode, and weighted mode methods. MR-Egger intercept test, MR-PRESSO test, Cochran’s Q test, funnel plots, and leaveone-out analysis were used to verify the validity and robustness of the MR results.ResultsIn the forward MR analysis of the IVW, genetically predicted HSV infections [odds ratio (OR) = 0.9917; 95% confidence interval (CI): 0.9685–1.0154; p = 0.4886], HSV keratitis and keratoconjunctivitis (OR = 0.9897; 95% CI: 0.9739–1.0059; p = 0.2107), anogenital HSV infection (OR = 1.0062; 95% CI: 0.9826–1.0304; p = 0.6081), VZV IgG (OR = 1.0003; 95% CI: 0.9849–1.0160; p = 0.9659), EBV IgG (OR = 0.9509; 95% CI: 0.8879–1.0183; p = 0.1497), CMV (OR = 0.9481; 95% CI: 0.8680–1.0357; p = 0.2374), HHV-6 IgG (OR = 0.9884; 95% CI: 0.9486–1.0298; p = 0.5765) and HHV-7 IgG (OR = 0.9991; 95% CI: 0.9693–1.0299; p = 0.9557) were not causally associated with ALS. The reverse MR analysis of the IVW revealed comparable findings, indicating no link between HHVs infections and ALS. The reliability and validity of the findings were verified by the sensitivity analysis.ConclusionAccording to the MR study, there is no evidence of causal associations between genetically predicted HHVs (HSV, VZV, EBV, CMV, HHV-6, and HHV-7) and ALS.

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“…Récemment, le GNbAC1, un anticorps dirigé contre la protéine d'enveloppe du HERV-W, a prouvé son efficacité en diminuant la transcription du rétrovirus mais aussi en prévenant son effet sur l'activation pro-inflammatoire des cellules immunitaires et sur la différenciation des oligodendrocytes [51][52][53]. En se fondant sur l'implication du HERV-W dans la SCZ et le TB, il semble donc possible d'espérer une stratégie thérapeutique dans ces pathologies neuropsychiatriques similaire à celle appliquée dans les maladies neurodégénératives comme la sclérose en plaque [54,55] (➜). D'autres études prenant en compte les nombreux facteurs de confusions évoqués et comprenant des cohortes de patients plus importantes sont nécessaires afin de comprendre le rôle que pourrait jouer HERV-W dans l'émergence de la SCZ et du TB.…”

Section: Discussionunclassified

“…Par ailleurs, il est intéressant de noter qu'une copie de HERV-W (HERV-W-Env) joue un rôle essentiel dans la physiologie humaine. En effet, une séquence, légèrement différente des autres séquences env de HERV-W, située sur la copie intégrée au chromosome 7q (locus ERVWE1), est hautement exprimée dans le placenta [55] (➜). Elle permet d'induire la fusion du cytotrophoblaste en syncytiotrophoblaste [17].…”

Section: Les Rétrovirus Endogènes Humainsunclassified

Les rétrovirus endogènes humains, une implication dans la schizophrénie et le trouble bipolaire

2017

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Des séquences rétrovirales endogènes dans le génome humain peuvent jouer un rôle physiologique ou pathologique

Cited by 9 publications

References 48 publications

An HERV-WENVtranscription in atypical memory B cells linked to COVID-19 evolution and risk for long COVID can express the encoded protein from a ribosome readthrough of mRNA from chromosome X

An HERV-WENVtranscription in atypical memory B cells linked to COVID-19 evolution and risk for long COVID can express the encoded protein from a ribosome readthrough of mRNA from chromosome X

Mendelian randomization analysis suggests no associations of human herpes viruses with amyotrophic lateral sclerosis

Les rétrovirus endogènes humains, une implication dans la schizophrénie et le trouble bipolaire

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