Role of Interleukin-2 and Herpes Simplex Virus 1 in Central Nervous System Demyelination in Mice
| Autor: | Kevin R. Mott, Mandana Zandian, Sariah J. Allen, Homayon Ghiasi |
|---|---|
| Rok vydání: | 2013 |
| Předmět: |
Central Nervous System
Interleukin 2 CNS demyelination Immunology Central nervous system Autoimmunity Herpesvirus 1 Human Biology Eye medicine.disease_cause Microbiology Immunoenzyme Techniques Optic neuropathy Interferon-gamma Mice Immune system Virology medicine Animals Interferon gamma Mice Inbred BALB C Herpes Simplex DNA medicine.disease Peptide Fragments Recombinant Proteins Mice Inbred C57BL medicine.anatomical_structure Herpes simplex virus Insect Science Keratitis Herpetic Optic nerve Interleukin-2 Pathogenesis and Immunity Female Demyelinating Diseases medicine.drug |
| Zdroj: | Journal of Virology. 87:12102-12109 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.02241-13 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|