+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Human endogenous retrovirus W in brain lesions: Rationale for targeted therapy in multiple sclerosis



Human endogenous retrovirus W in brain lesions: Rationale for targeted therapy in multiple sclerosis



Multiple Sclerosis and Related Disorders 8: 11-18



Attempts to identify a causative agent of Multiple Sclerosis (MS) among environmental viruses have consistently failed suggesting that development of MS is a result from gene-environment interactions. A new pathogenic player within human genes, a human endogenous retrovirus (HERV) was identified from MS cells, named MS-associated retrovirus element (MSRV) and unveiled homologous multicopy HERVs (HERV-W). As independent studies revealed biological features of HERV-W on immune-mediated inflammation and on remyelinating cells, the present study characterized the presence of HERV-W envelope protein (MSRV-Env) at the cellular level, in different MS lesion stages to extend and validate previous studies. Immunohistological analysis of HERV-W envelope cellular expression in different lesion stages from a cohort of MS brains versus controls, using well-characterized and highly specific monoclonal antibodies. HERV-W envelope protein was detected in all MS brains and quite essentially in lesions. Immunohistochemistry showed dominant expression in macrophages and microglia, coinciding with areas of active demyelination, spread over the active lesions, or limited to the rim of active microglia in chronic active lesions or in few surviving astrocytes of inactive plaques. Weak expression was seen in MS normal appearing white matter. In active plaques, few lymphoid cells and astrocytes were also stained. This HERV-W expression was not observed in control brains. HERV-W was expressed in demyelinated lesions from MS brains, which were all positive for this endogenous pathogenic protein. Pronounced HERV-W immunoreactivity in active MS lesions was intimately associated with areas of active demyelination throughout the successive stages of lesion evolution in MS brains. Based on its pathogenic potential, this HERV-W (MSRV) endogenous toxin thus appears to be a novel therapeutic target in MS. It also has a unique positioning as an early and lifelong expressed pathogenic agonist, acting upstream the pathways in which dysregulated physiological effectors are usually targeted by present therapeutic strategies for MS.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 058017551

Download citation: RISBibTeXText

PMID: 27456869

DOI: 10.1016/j.msard.2016.04.006


Related references

Human endogenous retrovirus (HERV)-W ENV and GAG proteins: physiological expression in human brain and pathophysiological modulation in multiple sclerosis lesions. Journal of Neurovirology 11(1): 23-33, 2005

Comprehensive analysis of human endogenous retrovirus group HERV-W locus transcription in multiple sclerosis brain lesions by high-throughput amplicon sequencing. Journal of Virology 87(24): 13837-13852, 2014

Multiple sclerosis-associated retrovirus and related human endogenous retrovirus-W in patients with multiple sclerosis: a literature review. Journal of Neuroimmunology 263(1-2): 8-12, 2013

Lack of immune responses against multiple sclerosis-associated retrovirus/human endogenous retrovirus W in patients with multiple sclerosis. Journal of Neurovirology 14(2): 143-151, 2008

Multiple sclerosis-associated retrovirus and related human endogenous retrovirus-W in patients with multiple sclerosis. Journal of Neuroimmunology 266(1-2): 87-88, 2014

Gene amplification of human endogenous retrovirus like sequences from brain tissue of multiple sclerosis patients and controls. FASEB Journal 5(6): A1661, 1991

Human endogenous retrovirus type W envelope expression in blood and brain cells provides new insights into multiple sclerosis disease. Multiple Sclerosis 18(12): 1721-1736, 2013

Analysis of transcribed human endogenous retrovirus W env loci clarifies the origin of multiple sclerosis-associated retrovirus env sequences. Retrovirology 6: 37, 2009

Brains and peripheral blood mononuclear cells of multiple sclerosis (MS) patients hyperexpress MS-associated retrovirus/HERV-W endogenous retrovirus, but not Human herpesvirus 6. Journal of General Virology 88(Pt 1): 264-274, 2006

An endogenous retrovirus with nucleic acid sequences similar to those of the multiple sclerosis associated retrovirus at the human T-cell receptor alpha, delta gene locus. Cellular and Molecular Biology 44(6): 927-931, 1998

Human endogenous retrovirus-K18 Env as a risk factor in multiple sclerosis. Multiple Sclerosis 14(9): 1175-1180, 2008

Human retrovirus involvement in amyotrophic lateral sclerosis a rationale for antiretroviral therapy?. Serratrice, G, Pouget, J, Blin, O, Figarella-Branger, D, Bille-Turc, F, Azulay, J - P, Pellissier, J - F, Advances in Neuromuscular Diseases: Nervous system, muscles and systemic diseases, Actualites Neuromusculaires: System nerveux, muscles et maladies systemiques: 250-263, 1993

Analysis of Human Endogenous Retrovirus Expression in Multiple Sclerosis Plaques. Journal of Emerging Diseases and Virology 3(2), 2017

Comparative expression of human endogenous retrovirus-W genes in multiple sclerosis. Aids Research and Human Retroviruses 23(10): 1251-1256, 2007

Multiple sclerosis, human T-lymphotropic virus type I, and human endogenous retrovirus sequences. Annals of Neurology 29(3): 343-344, 1991