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Antony, JM, van Marle, G, Opii, W, Butterfield, DA, Mallet, F, Yong, VW, Wallace, JL, Deacon, RM, Warren, K and Power, C (2004) Human endogenous retrovirus glycoprotein-mediated induction of redox reactants causes oligodendrocyte death and demyelination. Nat. Neurosci. 7:1088-95


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.


PubMed Online version:10.1038/nn1319


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



Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status


GO:0001948: glycoprotein binding



Figure 3

CACAO 9436

See also


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