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FASEB J. 2017 Jun;31(6):2267-2275. doi: 10.1096/fj.201601055R. Epub 2017 Feb 10.

Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Db class I molecule.

Author information

1
Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, Minnesota, USA.
2
Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA.
3
Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA.
4
Nuclear Magnetic Resonance Core Facility, Mayo Clinic, Rochester, Minnesota, USA.
5
Department of Immunology, Mayo Clinic, Rochester, Minnesota, USA; johnson.aaron2@mayo.edu.

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 Db class I molecule. FVB/Db and wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy via T2-weighted MRI and subsequent 3-dimensional volumetric analysis. Significant brain atrophy and hippocampal neuronal loss were observed in TMEV-infected FVB/Db mice, 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/Db mice 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-2Db class I molecule.

KEYWORDS:

CD8 T cells; MHC class I; TMEV; neurodegeneration; viral clearance

PMID:
28188174
PMCID:
PMC5434653
DOI:
10.1096/fj.201601055R
[Indexed for MEDLINE]
Free PMC Article

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