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Author Spotlight: Novel Assay for Studying B-Cell Responses in Multiple Sclerosis Research
Published on: December 1, 2023
The retrovirus/superantigen hypothesis of multiple sclerosis
Alexander Emmer1, Martin S Staege, Malte E Kornhuber
1Department of Neurology, Martin-Luther-University Halle-Wittenberg, Halle (Saale), Germany, alexander.emmer@uk-halle.de.
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.
Insights
Human endogenous retroviruses (HERV) may offer a new explanation for multiple sclerosis (MS) pathogenesis. HERV activation in the central nervous system (CNS) could drive both neurodegeneration and inflammation, suggesting novel therapeutic targets.
Area of Science:
- Neuroimmunology
- Virology
- Neurology
Background:
- The exact cause of multiple sclerosis (MS) remains unknown, with current theories focusing on autoimmune inflammation of the central nervous system (CNS).
- Neurodegeneration is typically considered a secondary effect in MS pathogenesis.
- This established view is being challenged by alternative hypotheses.
Purpose of the Study:
- To explore the potential role of human endogenous retroviruses (HERV) in the pathogenesis of multiple sclerosis (MS).
- To propose HERV-encoded envelope proteins (env) as potent immune stimulators (superantigens) within the CNS.
- To investigate HERV re-activation as a potential driver of both neurodegeneration and inflammatory relapses in MS.
Main Methods:
- Review of existing literature on HERV, superantigens, and MS.
- Analysis of proposed mechanisms for HERV-induced immune responses in the CNS.
- Comparison of experimental findings with clinical features of MS.
Main Results:
- Human endogenous retroviruses (HERV) can be activated within the CNS, with their envelope proteins acting as superantigens.
- Re-activation of HERV expression may directly induce neurodegeneration and slow disease progression.
- HERV-encoded superantigens could trigger inflammatory relapses in MS by activating T-cells and B-cells.
Conclusions:
- The hypothesis posits that HERV re-activation is a potential primary driver of multiple sclerosis (MS).
- HERV-encoded superantigens may explain the inflammatory relapses observed in MS.
- Targeting HERV offers a potential new avenue for MS therapy development.
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