Human endogenous retrovirus protein activates innate immunity and promotes experimental allergic encephalomyelitis in mice

PLoS One. 2013 Dec 6;8(12):e80128. doi: 10.1371/journal.pone.0080128. eCollection 2013.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adjuvants, Immunologic / administration & dosage
  • Animals
  • Cells, Cultured
  • Central Nervous System
  • Dendritic Cells
  • Disease Models, Animal*
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Gene Expression
  • Gene Products, env / administration & dosage*
  • Gene Products, env / immunology
  • Humans
  • Immunity, Innate / drug effects*
  • Lipopolysaccharide Receptors / genetics
  • Lipopolysaccharide Receptors / immunology
  • Mice*
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Multiple Sclerosis / genetics
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / pathology
  • Myelin-Oligodendrocyte Glycoprotein / administration & dosage
  • Peptide Fragments / administration & dosage
  • Pregnancy Proteins / administration & dosage*
  • Pregnancy Proteins / immunology
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / immunology
  • Toll-Like Receptor 4 / deficiency
  • Toll-Like Receptor 4 / genetics
  • Toll-Like Receptor 4 / immunology

Substances

  • Adjuvants, Immunologic
  • Gene Products, env
  • Lipopolysaccharide Receptors
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Pregnancy Proteins
  • Recombinant Proteins
  • TLR4 protein, human
  • Tlr4 protein, mouse
  • Toll-Like Receptor 4
  • myelin oligodendrocyte glycoprotein (35-55)
  • syncytin

Grant support

This study was funded by institutional support from INSERM and by grants from Fondation CERA-Lyon and AFM-ARSEP, France. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.