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

April M.Huseby Kelcher, Pascal A. Atanga, Jeffrey D. Gamez, Luz M.Cumba Garcia, Stephanie J. Teclaw, Kevin D. Pavelko, Slobodan I. Macura, Aaron J. Johnson

Research output: Contribution to journalArticle

2 Scopus citations

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 ofmajor 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 strongCD8T-cell response towardthe immunodominantDb-restrictedTMEV-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.

Original languageEnglish (US)
Pages (from-to)2267-2275
Number of pages9
JournalFASEB Journal
Volume31
Issue number6
DOIs
StatePublished - Jun 2017

Keywords

  • CD8 T cells
  • MHC class I
  • Neurodegeneration
  • TMEV
  • Viral clearance

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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    Kelcher, A. M. H., Atanga, P. A., Gamez, J. D., Garcia, L. M. C., Teclaw, S. J., Pavelko, K. D., Macura, S. I., & Johnson, A. J. (2017). Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Db class i molecule. FASEB Journal, 31(6), 2267-2275. https://doi.org/10.1096/fj.201601055R