A French group’s report of unexpected findings on endogenous retroviral elements expressed in cells from patients with MS appears to open a new avenue of research, after years of research dedicated to understanding the biological significance of retroviruses 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 MS. 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 the ongoing development of a neutralizing therapeutic antibody.

The group reviewed the pieces of a puzzle and now offer a consistent picture for the cause of MS. 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.

(Available from: http://www.pubmed.gov PMID: 19447411)

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