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J Neurol Sci. 2009 Nov 15;286(1-2):65-72. doi: 10.1016/j.jns.2009.04.034. Epub 2009 May 17.

Endogenous retroviral genes, Herpesviruses and gender in Multiple Sclerosis.

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GeNeuro, 14 Chemin des Aulx, CH-1228 Plan-Les Ouates, Geneva, Switzerland.


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.

[Indexed for MEDLINE]

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