title: Expression of HERV-Fc1, a human endogenous retrovirus, is increased in patients with active multiple sclerosis.
abstract: Multiple sclerosis (MS) is considered to be an autoimmune disease with an unknown cause and with immune system dysregulation. Among environmental factors, viruses are most often connected with the etiology of MS. Human endogenous retroviruses (HERVs) constitute 5 to 8% of human genomic DNA and have been detected as transcripts and proteins in the central nervous system (CNS) and peripheral blood, frequently in the context of neuroinflammation. HERV-Fc1, which belongs to the HERV-H/F family, has received our attention largely because of the genetic association with MS. We studied the expression of a capsid (Gag) protein of HERV-H/F origin by flow cytometry in peripheral blood mononuclear cells (PBMCs) from healthy controls and from MS patients with nonactive or active disease. There was a significant increase in HERV-H/F Gag expression in CD4(+) (P < 0.001) and CD8(+) (P < 0.001) T lymphocytes and in monocytes (P = 0.0356) in PBMCs from MS patients with active disease. Furthermore, we have undertaken the first rigorous SYBR green-based absolute quantitative PCR (Q-PCR) evaluation approach to quantify extracellular HERV-Fc1 RNA viral loads in plasma from MS patients and healthy controls. We found a 4-fold increase in extracellular HERV-Fc1 RNA titers in patients with active MS compared with healthy controls (P < 0.001). These findings strengthen the link between HERV-Fc1 and the pathology of MS. The cause and biological consequences of these differential expression levels will be the subject of further investigation. HERV-Fc1 biology could be a compelling area for understanding the pathology of MS and possibly other autoimmune disorders.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark. laska@humgen.au.dk
authors.forename: Magdalena Janina
authors.initials: MJ
authors.lastname: Laska
authors.forename: Tomasz
authors.initials: T
authors.lastname: Brudek
authors.forename: Kari Konstantin
authors.initials: KK
authors.lastname: Nissen
authors.forename: Tove
authors.initials: T
authors.lastname: Christensen
authors.forename: Anné
authors.initials: A
authors.lastname: Møller-Larsen
authors.forename: Thor
authors.initials: T
authors.lastname: Petersen
authors.forename: Bjørn Andersen
authors.initials: BA
authors.lastname: Nexø
mesh_terms: D000328:Adult; D020077:Endogenous Retroviruses / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D005260:Female; D015967:Gene Expression Regulation, Viral; D015683:Gene Products, gag / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology / Q000821:virology*; D013601:T-Lymphocytes / Q000821:virology; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D015683:Gene Products, gag