Endogenous retroviruses and multiple sclerosis–new pieces to the puzzle
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
BMC Neurology 2013, 13:111 doi:10.1186/1471-2377-13-111Published: 28 August 2013
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.