Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination

Joseph M. Antony, Guido Van Marle, Wycliffe Opii, D. Allan Butterfield, François Mallet, Voon Wee Yong, John L. Wallace, Robert M. Deacon, Kenneth Warren, Christopher Power

Research output: Contribution to journalArticlepeer-review

305 Scopus citations

Abstract

Human endogenous retroviruses (HERVs) constitute 8% of the human genome and have been implicated in both health and disease. Increased HERV gene activity occurs in immunologically activated glia, although the consequences of HERV expression in the nervous system remain uncertain. Here, we report that the HERV-W encoded glycoprotein syncytin is upregulated in glial cells within acute demyelinating lesions of multiple sclerosis patients. Syncytin expression in astrocytes induced the release of redox reactants, which were cytotoxic to oligodendrocytes. Syncytin-mediated neuroinflammation and death of oligodendrocytes, with the ensuing neurobehavioral deficits, were prevented by the antioxidant ferulic acid in a mouse model of multiple sclerosis. Thus, syncytin's proinflammatory properties in the nervous system demonstrate a novel role for an endogenous retrovirus protein, which may be a target for therapeutic intervention.

Original languageEnglish
Pages (from-to)1088-1095
Number of pages8
JournalNature Neuroscience
Volume7
Issue number10
DOIs
StatePublished - Oct 2004

Bibliographical note

Funding Information:
We thank P. Kubes, C. Hao and A. Clark for discussion; and C. Silva, A. Sullivan and A. Hood for technical assistance. J.M.A. holds a studentship from the Multiple Sclerosis Society of Canada (MSSC); G.v.M. is a Canadian Institutes of Health Research (CIHR)/Alberta Heritage Foundation for Medical Research (AHFMR) Fellow; V.W.Y. holds a Canada Research Chair (Tier 1) in neuroimmunology; J.L.W. is an AHFMR Scientist and C.P. is an AHFMR Scholar/CIHR Investigator. These studies were supported by the MSSC and CIHR Interdisciplinary Health Research Team (IHRT).

ASJC Scopus subject areas

  • Neuroscience (all)

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