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

doi:10.1038/nn1319

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

Nat Neurosci. 2004 Oct;7(10):1088-95. doi: 10.1038/nn1319. Epub 2004 Sep 26.

Authors

Joseph M Antony¹, Guido van Marle, Wycliffe Opii, D Allan Butterfield, François Mallet, Voon Wee Yong, John L Wallace, Robert M Deacon, Kenneth Warren, Christopher Power

Affiliation

¹ Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta T2N 4N1, Canada.

PMID: 15452578
DOI: 10.1038/nn1319

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Animals
Antioxidants / pharmacology
Antioxidants / therapeutic use
Astrocytes / immunology*
Astrocytes / metabolism
Astrocytes / virology
Cell Death / immunology
Cell Line
Coumaric Acids / pharmacology
Coumaric Acids / therapeutic use
Disease Models, Animal
Encephalitis / drug therapy
Encephalitis / immunology*
Encephalitis / virology
Endogenous Retroviruses / genetics
Endogenous Retroviruses / immunology
Endogenous Retroviruses / metabolism*
Gene Products, env / genetics
Gene Products, env / metabolism*
Humans
Mice
Middle Aged
Multiple Sclerosis / drug therapy
Multiple Sclerosis / immunology*
Multiple Sclerosis / virology
Myelin Sheath / metabolism
Oligodendroglia / immunology*
Oligodendroglia / metabolism
Oxidation-Reduction
Pregnancy Proteins / genetics
Pregnancy Proteins / metabolism*
RNA, Messenger / metabolism
Rats
Reactive Oxygen Species / antagonists & inhibitors
Reactive Oxygen Species / metabolism
Recombinant Fusion Proteins / pharmacology

Substances

Antioxidants
Coumaric Acids
Gene Products, env
Pregnancy Proteins
RNA, Messenger
Reactive Oxygen Species
Recombinant Fusion Proteins
syncytin
ferulic acid