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

• Published in: The FASEB journal Vol. 31; no. 6; p. 2267
• Main Authors: Huseby Kelcher, April M, Atanga, Pascal A, Gamez, Jeffrey D, Cumba Garcia, Luz M, Teclaw, Stephanie J, Pavelko, Kevin D, Macura, Slobodan I, Johnson, Aaron J
• Format: Journal Article
• Language: English
• Published: United States 01.06.2017
• Subjects: 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; MHC class I; neurodegeneration; viral clearance; TMEV; CD8 T cells
• ISSN: 1530-6860
• DOI: 10.1096/fj.201601055R

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 D class I molecule. FVB/D and wild-type FVB mice were evaluated for changes in neuroinflammation, virus clearance, neuropathology, and development of brain atrophy T2-weighted MRI and subsequent 3-dimensional volumetric analysis. Significant brain atrophy and hippocampal neuronal loss were observed in TMEV-infected FVB/D 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/D mice elicited a strong CD8 T-cell response toward the immunodominant D -restricted TMEV-derived peptide, VP2 , 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-2D class I molecule.