Letter to the editor

Garson, Jeremy A.; Créange, Alain; Dolei, Antonina; Ferrante, Pasquale; Jouvin‐Marche, Evelyne; Pn, Marche; Rieger, François; Ruprecht, Klemens; Saresella, Marina; Sotgiu, Stefano; Tedder, Richard S.; Perron, Hervé

doi:10.1191/1352458505ms1160xx

Cited by 13 publications

(2 citation statements)

References 10 publications

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“…The MSRV virion was the first member of the HERV-W family associated with MS and indeed the first member of the HERV-W family described [ 47 ]. The discovery of what initially appeared to be a new class of exogenous retrovirus provoked considerable debate and controversy regarding its origin which still persists at the present time [ 20 , 48 , 49 ]. For example, some authors have proposed that its origin could stem from the expression of isolated genes such as the one now known as ERVW1 , which encodes the cell-cell fusion protein syncytin-1 [ 46 ], while other research teams have suggested the existence of extracellular MSRV particles [ 50 ] or even possibly novel exogenous retrovirus as previously discussed [ 48 , 51 ].…”

Section: Disease Processes and Stimulation Of Herv Expressionmentioning

confidence: 99%

Do Human Endogenous Retroviruses Contribute to Multiple Sclerosis, and if So, How?

et al. 2018

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The gammaretroviral human endogenous retrovirus (HERV) families MRSV/HERV-W and HERV-H (including the closely related HERV-Fc1) are associated with an increased risk of multiple sclerosis (MS). Complete HERV sequences betray their endogenous retroviral origin, with open reading frames in gag, pro, pol and env being flanked by two long terminal repeats containing promoter and enhancer sequences with the capacity to regulate HERV transactivation and the activity of host genes in spite of endogenous epigenetic repression mechanisms. HERV virions, RNA, cDNA, Gag and Env, and antibodies to HERV transcriptional products, have variously been found in the blood and/or brain and/or cerebrospinal fluid of MS patients, with the HERV expression level being associated with disease status. Furthermore, some HERV-associated single nucleotide polymorphisms (SNPs), such as rs662139 T/C in a 3-kb region of Xq22.3 containing a HERV-W env locus, and rs391745, upstream of the HERV-Fc1 locus on the X chromosome, are associated with MS susceptibility, while a negative association has been reported with SNPs in the tripartite motif-containing (TRIM) protein-encoding genes TRIM5 and TRIM22. Factors affecting HERV transcription include immune activation and inflammation, since HERV promoter regions possess binding sites for related transcription factors; oxidative stress, with oxidation of guanine to 8-oxoguanine and conversion of cytosine to 5-hydroxymethylcytosine preventing binding of methyl groups transferred by DNA methyltransferases; oxidative stress also inhibits the activity of deacetylases, thereby favouring the acetylation of histone lysine residues favouring gene expression; interferon beta; natalizumab treatment; impaired epigenetic regulation; and the sex of patients.

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Section: Disease Processes and Stimulation Of Herv Expressionmentioning

confidence: 99%

Do Human Endogenous Retroviruses Contribute to Multiple Sclerosis, and if So, How?

et al. 2018

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“…Concerning the HERV-W family and its virion-associated MSRV element, an association with multiple sclerosis has been repeatedly and independently demonstrated over the past two decades [12], [18], [20], [21], [22], [23], [24], [25], [26], [27].…”

Section: Introductionmentioning

confidence: 99%

Human Endogenous Retrovirus Protein Activates Innate Immunity and Promotes Experimental Allergic Encephalomyelitis in Mice

et al. 2013

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Multiple sclerosis (MS) is a complex multifactorial disease of the central nervous system (CNS) for which animal models have mainly addressed downstream immunopathology but not potential inducers of autoimmunity. In the absence of a pathogen known to cause neuroinflammation in MS, Mycobacterial lysate is commonly used in the form of complete Freund's adjuvant to induce autoimmunity to myelin proteins in Experimental Allergic Encephalomyelitis (EAE), an animal model for MS. The present study demonstrates that a protein from the human endogenous retrovirus HERV-W family (MSRV-Env) can be used instead of mycobacterial lysate to induce autoimmunity and EAE in mice injected with MOG, with typical anti-myelin response and CNS lesions normally seen in this model. MSRV-Env was shown to induce proinflammatory response in human macrophage cells through TLR4 activation pathway. The present results demonstrate a similar activation of murine dendritic cells and show the ability of MSRV-Env to trigger EAE in mice. In previous studies, MSRV-Env protein was reproducibly detected in MS brain lesions within microglia and perivascular macrophages. The present results are therefore likely to provide a model for MS, in which the upstream adjuvant triggering neuroinflammation is the one detected in MS active lesions. This model now allows pre-clinical studies with therapeutic agents targeting this endogenous retroviral protein in MS.

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The Human Endogenous Retrovirus Link between Genes and Environment in Multiple Sclerosis and in Multifactorial Diseases Associating Neuroinflammation

Perron¹,

Lang²

2009

Clinic Rev Allerg Immunol

131

118

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Endogenous retroviruses represent about 8% of the human genome and belong to the superfamily of transposable and retrotransposable genetic elements. Altogether, these mobile genetic elements and their numerous inactivated "junk" sequences represent nearly one half of the human DNA. Nonetheless, a significant part of this "non-conventional" genome has retained potential activity. Epigenetic control is notably involved in silencing most of these genetic elements but certain environmental factors such as viruses are known to dysregulate their expression in susceptible cells. More particularly, embryonal cells with limited gene methylation are most susceptible to uncontrolled activation of these mobile genetic elements by, e.g., viral infections. In particular, certain viruses transactivate promoters from endogenous retroviral family type W (HERV-W). HERV-W RNA was first isolated in circulating viral particles (Multiple Sclerosis-associated RetroViral element, MSRV) that have been associated with the evolution and prognosis of multiple sclerosis. HERV-W elements encode a powerful immunopathogenic envelope protein (ENV) that activates a pro-inflammatory and autoimmune cascade through interaction with Toll-like receptor 4 on immune cells. This ENV protein has repeatedly been detected in MS brain lesions and may be involved in other diseases. Epigenetic factors controlling HERV-W ENV protein expression then reveal critical. This review addresses the gene-environment epigenetic interface of such HERV-W elements and its potential involvement in disease.

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Letter to the editor

Cited by 13 publications

References 10 publications

Do Human Endogenous Retroviruses Contribute to Multiple Sclerosis, and if So, How?

Do Human Endogenous Retroviruses Contribute to Multiple Sclerosis, and if So, How?

Human Endogenous Retrovirus Protein Activates Innate Immunity and Promotes Experimental Allergic Encephalomyelitis in Mice

The Human Endogenous Retrovirus Link between Genes and Environment in Multiple Sclerosis and in Multifactorial Diseases Associating Neuroinflammation

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