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

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

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Intramural
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Atrophy
  • Brain / pathology*
  • Brain / virology
  • Brain Diseases / virology*
  • CD8-Positive T-Lymphocytes / physiology
  • Disease Models, Animal
  • Gene Expression Regulation
  • Genes, MHC Class I / genetics*
  • Mice
  • Mice, Inbred Strains
  • Mice, Transgenic
  • Neurons / virology
  • Picornaviridae Infections / immunology
  • Picornaviridae Infections / pathology*
  • Theilovirus*
  • Viral Load