title: A unifying multiple sclerosis etiology linking virus infection, sunlight, and vitamin D, through viral interleukin-10.
abstract: Multiple sclerosis (MS) is a neurodegenerative disease of uncertain etiology. In MS, neurodegeneration is thought to be secondary to autoimmune-mediated damage. However, no cohesive explanation yet exists as to how environmental factors interact to induce a neurodegenerative autoimmune response. Insufficient sunlight exposure and chronic viral infections have been proposed as unrelated environmental risk factors for MS. We suggest that these risk factors may act synergistically to enable the pathogenic autoimmune response. Low ultraviolet light (UVL) exposure depletes vitamin D3 stores, and low vitamin D3 levels correlate strongly with high MS risk. The central nervous system converts vitamin D3 into 1,25-dihydroxyvitamin D3 (1,25-(OH)2 D3), a biologically active hormone with anti-inflammatory and neuro-protective functions that depend on IL-10-producing regulatory lymphocytes. Herpesvirus infection also correlates with MS risk. Some herpesviruses like Epstein-Barr virus produce an IL-10-like cytokine termed vIL-10. We hypothesize that vIL-10 may induce a dysfunction of IL-10-producing regulatory lymphocytes, thereby undermining the protective functions of sunlight, vitamin D3, and 1,25-(OH)2 D3. The vIL-10 could elicit a host immune response capable of neutralizing or depleting IL-10, or the vIL-10 could compete with IL-10 but fail to perform an essential IL-10 function. In either case, the lack of sunlight exposure and the herpes virus infection might synergize to induce a defect in IL-10-producing regulatory lymphocyte function that undermines self-tolerance mechanisms and enables a pathogenic autoimmune response to neural proteins.
authors.affiliation: Department of Biochemistry, University of Wisconsin, Madison, 433 Babcock Drive, Madison, WI 53706, USA. hayes@biochem.wisc.edu
authors.forename: Colleen E
authors.initials: CE
authors.lastname: Hayes
authors.forename: E
authors.initials: E
authors.lastname: Donald Acheson
mesh_terms: D006564:Herpesviridae / Q000276:immunology / Q000472:pathogenicity*; D006566:Herpesviridae Infections / Q000150:complications / Q000276:immunology; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000209:etiology* / Q000276:immunology / Q000821:virology; D017634:Self Tolerance; D013472:Sunlight; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D014807:Vitamin D / Q000378:metabolism; D014808:Vitamin D Deficiency / Q000150:complications
chemical_list: D016753:Interleukin-10; D014807:Vitamin D