Human endogenous retrovirus W envelope induces a preclinical multiple sclerosis model in C57/B16 myelin oligodendrocyte glycoprotein mouse: therapeutic effect of monoclonal antibody
Background: The human endogenous retroviral family W (HERV-W) encodes a powerful imunopathogenic envelope protein (ENV), which activates a pro-inflammatory and autoimmune cascade through interaction with Toll-Like receptor 4 (TLR4) on antigen-presenting cells and triggers superantigen-like dysregula...
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Published in | Multiple sclerosis Vol. 14; p. S87 |
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Main Authors | , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
01.09.2008
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Subjects | |
Online Access | Get full text |
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Summary: | Background: The human endogenous retroviral family W (HERV-W) encodes a powerful imunopathogenic envelope protein (ENV), which 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-lymphocvtes. The specific association of HERV-W RNA in circulating virion particles (multiple sclerosis-associated retroviral element, MSRV) with multiple sclerosis (MS), its evolution and prognosis has now been repeatedly reported. Its ENV protein was evidenced by several independent PCR and/or immunohistological studies in MS brain lesions post-mortem. ELISA immunodosage for HERV-W ENV protein revealed positive anti genemia in 73% of MS sera and a low percentage ( similar to S%) of asymptomatic or healthy carriers in the normal population, suggesting that HERV-W ENV antigenemia is not simply a consequence of MS (manuscript submitted). Objective: To study the effects of HERV-W ENV protein compared with classical EAE in the C57/B16 mouse model. To evaluate the pre-clinical therapeutic effects of a neutralising monoclonal antibody against HERV-W ENV. Methods: Magnetic resonance imaging (MRI) follow-up, immunohistochemistry, immunoassays. Results: HERV-W ENV protein is here shown to reproduce the experimental autoimmune encephalomyelitis animal model in CS7/B16 mice with important inflammatory demyelination and gliosis evidenced by MRI and histology, as well as anti-myelin autoimmunity. A significant inhibition and prevention of clinical symptoms, compared with untreated controls, were evidenced in this pre-clinical model by clinical and MRI follow-up, when injecting selected anti-HERV/ENV antibody in mice with ongoing central nervous system inflammation and clinical deficits. Untreated ENV EAE ill-control mice died or reached major neurological deficit. Conclusions: This model is thus useful for pre-clinical evaluations and these new results now pave the way for the assessment of a therapeutic version of this anti-ENV antibody. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 content type line 23 ObjectType-Feature-2 |
ISSN: | 1352-4585 |