Brain atrophy in picornavirus‐infected FVB mice is dependent on the H‐2Db class I molecule. Issue 6 (10th February 2017)

• Record Type: Journal Article
• Authors: Huseby Kelcher, April M.; Atanga, Pascal A.; Gamez, Jeffrey D.; Garcia, Luz M. Cumba; Teclaw, Stephanie J.; Pavelko, Kevin D.; Macura, Slobodan I.; Johnson, Aaron J.
• Is Part Of: FASEB journal. Volume 31:Issue 6(2017)
• Page Start: 2267
• Page End: 2275
• Publication Date: 2017-02-10
• Subjects: neurodegeneration -- MHC class I -- viral clearance -- TMEV -- CD8 T cells; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.201601055R
• Languages: English
• ISSNs: 0892-6638

Abstract

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 D b class I molecule. FVB/D b 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/D b 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 b mice elicited a strong CD8 T‐cell response toward the immunodominant D b ‐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. FASEB J. 31, 2267–2275 (2017). www.fasebj.org