Endogenous retroviral genes, Herpesviruses and gender in Multiple Sclerosis.

Abstract

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.

• Authors: Hervé Perron, Corinne Bernard, Jean-Baptiste Bertrand, Alois B Lang, Iuliana Popa, Kamel Sanhadji, Jacques Portoukalian
• Journal: Journal of the neurological sciences (J Neurol Sci) Vol. 286 Issue 1-2 Pg. 65-72 (Nov 15 2009) ISSN: 1878-5883 [Electronic] Netherlands
• PMID: 19447411 (Publication Type: Journal Article, Review)

Chemical References

• Gene Products, env
• Toll-Like Receptor 4

Topics

• Animals
• Antigen-Presenting Cells (immunology, metabolism)
• Chromosomes, Human, X
• Endogenous Retroviruses (genetics, immunology, isolation & purification)
• Female
• Gene Products, env (immunology, metabolism)
• Herpesviridae (genetics, immunology, pathogenicity)
• Humans
• Male
• Multiple Sclerosis (etiology, genetics, virology)
• Sex Factors
• Toll-Like Receptor 4 (genetics, metabolism)