Endogenous retroviral genes, Herpesviruses and gender in Multiple Sclerosis.
Unexpected findings on endogenous retroviral elements expressed in cells from patients with Multiple Sclerosis appear to open a new avenue of research, after years of research dedicated to the understanding of their biological significance in human health and disease. Human endogenous retroviral family W (HERV-W) RNA present in circulating viral particles (Multiple Sclerosis associated RetroViral element, MSRV) has 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 (TLR4) on antigen-presenting cells, and triggers superantigen-like dysregulation of T-lymphocytes. HERV-W/ENV antigen has further been shown to be an upstream inducer of immunopathogenicity like that in MS and has repeatedly been detected in association with MS lesions in post-mortem brain studies. ENV protein now represents a novel target in MS, in our ongoing development of a neutralising therapeutic antibody. We here review the pieces of a puzzle, which now offer a consistent picture for Multiple Sclerosis aetiopathogenesis. Interestingly, at the gene-environment interface, this picture also includes gender-related specificities through the potential interplay with endogenous retrovirus type W copies present on the X chromosome.
Perron
Hervé
H
GeNeuro, 14 Chemin des Aulx, CH-1228 Plan-Les Ouates, Geneva, Switzerland.
Bernard
Corinne
C
Bertrand
Jean-Baptiste
JB
Lang
Alois B
AB
Popa
Iuliana
I
Sanhadji
Kamel
K
Portoukalian
Jacques
J
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D041321:Chromosomes, Human, X; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification; D005260:Female; D015686:Gene Products, env / Q000276:immunology / Q000378:metabolism; D006564:Herpesviridae / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000209:etiology / Q000235:genetics / Q000821:virology; D012737:Sex Factors; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
D015686:Gene Products, env; D051197:Toll-Like Receptor 4