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The Retrovirus/Superantigen Hypothesis of Multiple Sclerosis

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Abstract

The pathogenesis of multiple sclerosis (MS) is as yet unknown. Commonly, MS is assumed to be due to an autoimmune inflammation of the central nervous system (CNS). Neurodegeneration is regarded to be a secondary reaction. This concept is increasingly being challenged. Human endogenous retroviruses (HERV) that could be locally activated in the CNS have been proposed as an alternative concept. HERV-encoded envelope proteins (env) can act as strong immune stimulators (superantigens). Thus, slow disease progression following neurodegeneration might be induced by re-activation of HERV expression directly, while relapses in parallel to inflammation might be secondary to the expression of HERV-encoded superantigens. It has been shown previously that T-cell superantigens are capable to induce a cellular inflammatory reaction in the CNS of experimental animals similar to that in MS. Furthermore, B-cell superantigens have been shown to activate blood leucocytes in vitro to produce immunoglobulin in an oligoclonal manner. It remains to be established, whether the outlined hypothesis accords with all known features of MS. Furthermore, anti-HERV agents may be taken into consideration to enrich and improve MS therapy.

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Acknowledgments

A. E. and M. S. S. are supported by the Wilhelm-Roux program (FKZ 21/22, FKZ 25/28, and FKZ 25/22) of the University of Halle-Wittenberg. Furthermore, we gratefully acknowledge generous support by Novartis Pharma GmbH.

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  1. Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

    Alexander Emmer & Malte E. Kornhuber

  2. Department of Pediatrics, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany

    Martin S. Staege

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  1. Alexander Emmer
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  2. Martin S. Staege
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Correspondence to Alexander Emmer.

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Emmer, A., Staege, M.S. & Kornhuber, M.E. The Retrovirus/Superantigen Hypothesis of Multiple Sclerosis. Cell Mol Neurobiol 34, 1087–1096 (2014). https://doi.org/10.1007/s10571-014-0100-7

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