title: Endogenous retroviruses and multiple sclerosis-new pieces to the puzzle.
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.
authors.affiliation: Department of Biomedicine, Aarhus University, Wilhelm Meyers Allé 4, DK-8000, Aarhus, C, Denmark. nexo@hum-gen.au.dk.
authors.forename: Kari K
authors.initials: KK
authors.lastname: Nissen
authors.forename: Magdalena J
authors.initials: MJ
authors.lastname: Laska
authors.forename: Bettina
authors.initials: B
authors.lastname: Hansen
authors.forename: Thorkild
authors.initials: T
authors.lastname: Terkelsen
authors.forename: Palle
authors.initials: P
authors.lastname: Villesen
authors.forename: Shervin
authors.initials: S
authors.lastname: Bahrami
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.forename: Finn S
authors.initials: FS
authors.lastname: Pedersen
authors.forename: Bjørn A
authors.initials: BA
authors.lastname: Nexø
mesh_terms: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins / Q000235:genetics; D020077:Endogenous Retroviruses / Q000235:genetics* / Q000472:pathogenicity*; D005819:Genetic Markers; D006801:Humans; D009103:Multiple Sclerosis / Q000235:genetics* / Q000821:virology; D000070584:Tripartite Motif Proteins; D044767:Ubiquitin-Protein Ligases
chemical_list: D000090103:Antiviral Restriction Factors; D002352:Carrier Proteins; D005819:Genetic Markers; D000070584:Tripartite Motif Proteins; C477346:TRIM5 protein, human; D044767:Ubiquitin-Protein Ligases