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 Citations (Scopus)

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 1 2017

Fingerprint

Picornaviridae
Viruses
Atrophy
Brain
Theilovirus
Molecules
T-cells
Volumetric analysis
T-Lymphocytes
Demyelinating Diseases
Virus Diseases
Nervous System Diseases
Major Histocompatibility Complex
Magnetic resonance imaging
Transgenic Mice
Neurons
Fluorescent Antibody Technique
Observation
Peptides

Keywords

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

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

Kelcher, A. M. H., Atanga, P. A., Gamez, J. D., Garcia, L. M. C., Teclaw, S. J., Pavelko, K. D., ... 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

Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Db class i molecule. / Kelcher, April M.Huseby; Atanga, Pascal A.; Gamez, Jeffrey D.; Garcia, Luz M.Cumba; Teclaw, Stephanie J.; Pavelko, Kevin D.; Macura, Slobodan I; Johnson, Aaron J.

In: FASEB Journal, Vol. 31, No. 6, 01.06.2017, p. 2267-2275.

Research output: Contribution to journalArticle

Kelcher, AMH, Atanga, PA, Gamez, JD, Garcia, LMC, Teclaw, SJ, Pavelko, KD, Macura, SI & Johnson, AJ 2017, 'Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Db class i molecule', FASEB Journal, vol. 31, no. 6, pp. 2267-2275. https://doi.org/10.1096/fj.201601055R
Kelcher AMH, Atanga PA, Gamez JD, Garcia LMC, Teclaw SJ, Pavelko KD et al. Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Db class i molecule. FASEB Journal. 2017 Jun 1;31(6):2267-2275. https://doi.org/10.1096/fj.201601055R
Kelcher, April M.Huseby ; Atanga, Pascal A. ; Gamez, Jeffrey D. ; Garcia, Luz M.Cumba ; Teclaw, Stephanie J. ; Pavelko, Kevin D. ; Macura, Slobodan I ; Johnson, Aaron J. / Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Db class i molecule. In: FASEB Journal. 2017 ; Vol. 31, No. 6. pp. 2267-2275.
@article{e9e1552c48504f1380035dad30155a4d,
title = "Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Db class i molecule",
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.",
keywords = "CD8 T cells, MHC class I, Neurodegeneration, TMEV, Viral clearance",
author = "Kelcher, {April M.Huseby} and Atanga, {Pascal A.} and Gamez, {Jeffrey D.} and Garcia, {Luz M.Cumba} and Teclaw, {Stephanie J.} and Pavelko, {Kevin D.} and Macura, {Slobodan I} and Johnson, {Aaron J.}",
year = "2017",
month = "6",
day = "1",
doi = "10.1096/fj.201601055R",
language = "English (US)",
volume = "31",
pages = "2267--2275",
journal = "FASEB Journal",
issn = "0892-6638",
publisher = "FASEB",
number = "6",

}

TY - JOUR

T1 - Brain atrophy in picornavirus-infected FVB mice is dependent on the H-2Db class i molecule

AU - Kelcher, April M.Huseby

AU - Atanga, Pascal A.

AU - Gamez, Jeffrey D.

AU - Garcia, Luz M.Cumba

AU - Teclaw, Stephanie J.

AU - Pavelko, Kevin D.

AU - Macura, Slobodan I

AU - Johnson, Aaron J.

PY - 2017/6/1

Y1 - 2017/6/1

N2 - 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.

AB - 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.

KW - CD8 T cells

KW - MHC class I

KW - Neurodegeneration

KW - TMEV

KW - Viral clearance

UR - http://www.scopus.com/inward/record.url?scp=85020313002&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85020313002&partnerID=8YFLogxK

U2 - 10.1096/fj.201601055R

DO - 10.1096/fj.201601055R

M3 - Article

C2 - 28188174

AN - SCOPUS:85020313002

VL - 31

SP - 2267

EP - 2275

JO - FASEB Journal

JF - FASEB Journal

SN - 0892-6638

IS - 6

ER -