MSRV envelope protein is a potent, endogenous and pathogenic agonist of human toll-like receptor 4: Relevance of GNbAC1 in multiple sclerosis treatment
- PMID: 26857492
- DOI: 10.1016/j.jneuroim.2015.12.006
MSRV envelope protein is a potent, endogenous and pathogenic agonist of human toll-like receptor 4: Relevance of GNbAC1 in multiple sclerosis treatment
Abstract
Multiple sclerosis associated retrovirus envelope protein (MSRV-Env) was repeatedly detected in brain lesions and blood of multiple sclerosis (MS) patients. We performed the first pharmacological characterisation of MSRV-Env on recombinant and native human TLR4. MSRV-Env is a full and highly potent TLR4 agonist of endogenous origin. MSRV-Env induces TLR4-dependent pro-inflammatory stimulation of immune cells in vitro and in vivo, and impairs oligodendrocytes precursor cells differentiation to myelinating oligodendrocytes. MSRV-Env may play a role in chronic inflammation and impaired remyelination in MS. GNbAC1, a selective monoclonal antibody, antagonizes MSRV-Env pathogenic effects and represents an innovative therapeutic approach of MS.
Keywords: GNbAC1; HERV-W; MSRV envelope; Monoclonal antibody; Multiple sclerosis; TLR4.
Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
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