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Open Access Highly Accessed Review

Endogenous retroviruses and multiple sclerosis–new pieces to the puzzle

Kari K Nissen1, Magdalena J Laska1, Bettina Hansen1, Thorkild Terkelsen1, Palle Villesen2, Shervin Bahrami3, Thor Petersen4, Finn S Pedersen5 and Bjørn A Nexø1*

Author Affiliations

1 Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, DK-8000, Aarhus, C, Denmark

2 Bioinformatics Research Centre, Aarhus University, C.F.Møllers Allé 8, DK-8000, Aarhus, C, Denmark

3 SKAUvaccines, Incuba Science Park, Åbogade 15, DK-8200, Aarhus, N, Denmark

4 Department of Neurology, Aarhus University Hospital, Nørrebrogade 44, DK-8000, Aarhus, C, Denmark

5 Department of Molecular Biology and Genetics, Aarhus University, C.F.Møllers Allé 3, DK-8000, Aarhus, C, Denmark

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BMC Neurology 2013, 13:111  doi:10.1186/1471-2377-13-111

Published: 28 August 2013

Abstract

The possibility that retroviruses play a role in multiple sclerosis (MS) has long been considered; accumulating findings suggest this to be most likely in the form of human endogenous retroviruses (HERVs). A genetic test series of fifty endogenous retroviral loci for association with MS in Danes showed SNP markers near a specific endogenous retroviral locus, HERV-Fc1 located on the X-chromosome, to be positive. Bout Onset MS was associated with the HERV-Fc1 locus, while a rarer form, Primary Progressive MS, was not. Moreover, HERV-Fc1 Gag RNA in plasma was increased 4-fold in patients with recent history of attacks, relative to patients in a stable state and to healthy controls.

Finally, genetic variations in restriction genes for retroviruses influence the risk of MS, providing further support for a role of retroviral elements in disease.

We speculate that endogenous retroviruses may activate the innate immune system in a variety of ways, involving the host proteins, TRIMs, TLRs, TREXs and STING. Observations in HIV-positive patients suggest that antiretroviral drugs can curb MS. Thus, these new findings regarding the etiology and pathogenesis of MS, suggest alternative ways to challenge autoimmune diseases.

Keywords:
Multiple sclerosis; Endogenous retroviruses; HERV-Fc1; TRIM; BST2; Genetic association