title: Role of interleukin-2 and herpes simplex virus 1 in central nervous system demyelination in mice.
abstract: We have reported previously that ocular infection of different strains of mice with recombinant herpes simplex virus 1 (HSV-1) constitutively expressing interleukin-2 (IL-2) provokes central nervous system (CNS) demyelination and optic neuropathy, as determined by changes in visual evoked cortical potentials and pathological changes in the optic nerve and CNS, whereas recombinant viruses expressing IL-4, gamma interferon, IL-12p35, IL-12p40, or IL-12p70 do not induce this neuropathy. The goal of this study was to dissect the mechanism underlying the interplay between the immune system (elevation of IL-2) and an environmental factor (infection with HSV-1) that elicits this pathology. Similar results were obtained upon delivery of IL-2 into the mouse brain using osmotic minipumps or injection of mice with recombinant IL-2 protein, IL-2 DNA, or IL-2 synthetic peptides prior to infection with wild-type (wt) HSV-1 strains McKrae and KOS. The critical role of IL-2 is further supported by our data, indicating that a single mutation at position T27A in IL-2 completely blocks the HSV-1-induced pathology. This study shows a novel model of autoimmunity in which viral infection and enhanced IL-2 cause CNS demyelination.
authors.affiliation: Center for Neurobiology and Vaccine Development, Ophthalmology Research, Department of Surgery, Cedars-Sinai Medical Center, Los Angeles, California, USA.
authors.forename: Kevin R
authors.initials: KR
authors.lastname: Mott
authors.forename: Mandana
authors.initials: M
authors.lastname: Zandian
authors.forename: Sariah J
authors.initials: SJ
authors.lastname: Allen
authors.forename: Homayon
authors.initials: H
authors.lastname: Ghiasi
mesh_terms: D000818:Animals; D015551:Autoimmunity; D002490:Central Nervous System / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D004247:DNA / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism; D003711:Demyelinating Diseases / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D005123:Eye / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D005260:Female; D006561:Herpes Simplex / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D018259:Herpesvirus 1, Human / Q000235:genetics; D007124:Immunoenzyme Techniques; D007371:Interferon-gamma / Q000378:metabolism; D007376:Interleukin-2 / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D016849:Keratitis, Herpetic / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010446:Peptide Fragments / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007376:Interleukin-2; D010446:Peptide Fragments; D011994:Recombinant Proteins; D007371:Interferon-gamma; D004247:DNA