title: Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Dbclass I molecule.
abstract: Brain atrophy is a common feature of numerous neurologic diseases in which the role of neuroinflammation remains ill-defined. In this study, we evaluated the contribution of major histocompatibility complex class I molecules to brain atrophy in Theiler's murine encephalomyelitis virus (TMEV)-infected transgenic FVB mice that express the Dbclass I molecule. FVB/Dband wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophyviaT2-weighted MRI and subsequent 3-dimensional volumetric analysis. Significant brain atrophy and hippocampal neuronal loss were observed in TMEV-infected FVB/Dbmice, but not in wild-type FVB mice. Brain atrophy was observed at 1 mo postinfection and persisted through the 4-mo observation period. Of importance, virus-infected FVB/Dbmice elicited a strong CD8 T-cell response toward the immunodominant Db-restricted TMEV-derived peptide, VP2121-130, and cleared TMEV from the CNS. In addition, immunofluorescence revealed CD8 T cells near virus-infected neurons; therefore, we hypothesize that class I restricted CD8 T-cell responses promote development of brain atrophy. This model provides an opportunity to analyze the contribution of immune cells to brain atrophy in a system where persistent virus infection and demyelination are not factors in long-term neuropathology.-Huseby Kelcher, A. M., Atanga, P. A., Gamez, J. D., Cumba Garcia, L. M., Teclaw, S. J., Pavelko, K. D., Macura, S. I., Johnson. A. J. Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Dbclass I molecule.
authors.affiliation: Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota, USA.|Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: April M
authors.initials: AM
authors.lastname: Huseby Kelcher
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Pascal A
authors.initials: PA
authors.lastname: Atanga
authors.affiliation: Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Gamez
authors.affiliation: Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota, USA.|Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Luz M
authors.initials: LM
authors.lastname: Cumba Garcia
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Stephanie J
authors.initials: SJ
authors.lastname: Teclaw
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Pavelko
authors.affiliation: Nuclear Magnetic Resonance Core Facility, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Slobodan I
authors.initials: SI
authors.lastname: Macura
authors.affiliation: Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA; johnson.aaron2@mayo.edu.|Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
authors.forename: Aaron J
authors.initials: AJ
authors.lastname: Johnson
mesh_terms: D000818:Animals; D001284:Atrophy; D001921:Brain / Q000473:pathology* / Q000821:virology; D001927:Brain Diseases / Q000821:virology*; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005805:Genes, MHC Class I / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D008822:Mice, Transgenic; D009474:Neurons / Q000821:virology; D010850:Picornaviridae Infections / Q000276:immunology / Q000473:pathology*; D017945:Theilovirus; D019562:Viral Load
keywords: CD8 T cells; MHC class I; TMEV; neurodegeneration; viral clearance