Human Endogenous Retrovirus Protein Activates Innate Immunity and Promotes Experimental Allergic Encephalomyelitis in Mice

Abstract

Multiple sclerosis (MS) is a complex multifactorial disease of the central nervous system (CNS) for which animal models have mainly addressed downstream immunopathology but not potential inducers of autoimmunity. In the absence of a pathogen known to cause neuroinflammation in MS, Mycobacterial lysate is commonly used in the form of complete Freund's adjuvant to induce autoimmunity to myelin proteins in Experimental Allergic Encephalomyelitis (EAE), an animal model for MS. The present study demonstrates that a protein from the human endogenous retrovirus HERV-W family (MSRV-Env) can be used instead of mycobacterial lysate to induce autoimmunity and EAE in mice injected with MOG, with typical anti-myelin response and CNS lesions normally seen in this model. MSRV-Env was shown to induce proinflammatory response in human macrophage cells through TLR4 activation pathway. The present results demonstrate a similar activation of murine dendritic cells and show the ability of MSRV-Env to trigger EAE in mice. In previous studies, MSRV-Env protein was reproducibly detected in MS brain lesions within microglia and perivascular macrophages. The present results are therefore likely to provide a model for MS, in which the upstream adjuvant triggering neuroinflammation is the one detected in MS active lesions. This model now allows pre-clinical studies with therapeutic agents targeting this endogenous retroviral protein in MS.

The aliens inside us: HERV-W endogenous retroviruses and multiple sclerosis

“…12 MSRVenv alone was shown to promote experimental allergic encephalomyelitis (EAE) in mice, that is, the animal model of human MS. 21 If the mice with full-blown EAE were treated with an anti-HERV-Wenv protein monoclonal antibody, a reversal of clinical score kinetics toward healing was observed, while all untreated animals died (or had to be euthanized because of complete paralysis). 22 …”

Multiple Sclerosis and Subsequent Human Immunodeficiency Virus Infection: A Case with the Rare Comorbidity, Focus on Novel Treatment Issues and Review of the Literature

“…Another explanation regarding the clinical stability of all patients reported is that antiretroviral medications used to suppress HIV replication, in theory, may suppress other viral pathogens implicated in MS, like Human Endogenous Retroviruses (HERVs) and herpes viruses (32)(33)(34)(35)(36)(37).…”

Des séquences rétrovirales endogènes dans le génome humain peuvent jouer un rôle physiologique ou pathologique

“…dendritiques, une réponse auto-immune anti-myéline et peut induire une encéphalomyélite auto-immune expérimentale dans le modèle animal expérimental de la SEP [30]. MSRV-Env agit également sur les cellules endothéliales vasculaires cérébrales, qui expriment TLR4, affectant la perméabilité vasculaire et l'expression de récepteurs d'adhésion cellulaire (ICAM-1, intercellular adhesion molecule 1), ce qui contribue à l'invasion du système nerveux par les leucocytes circulants [31].…”