Pathogenic role for virus-specific CD4 T cells in mice with coronavirus-induced acute encephalitis

Daniela Anghelina; Lecia Pewe; Stanley Perlman

doi:10.2353/ajpath.2006.051308

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Pathogenic role for virus-specific CD4 T cells in mice with coronavirus-induced acute encephalitis

Journal article

Open access

Peer reviewed

Pathogenic role for virus-specific CD4 T cells in mice with coronavirus-induced acute encephalitis

Daniela Anghelina, Lecia Pewe and Stanley Perlman

The American journal of pathology, Vol.169(1), pp.209-222

07/2006

DOI: 10.2353/ajpath.2006.051308

PMCID: PMC1698761

PMID: 16816374

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Abstract

Acute viral encephalitis is believed to result from direct virus destruction of infected cells and from virus-induced host immune response, but the relative contribution of each remains largely unknown. For example, C57BL/6 (B6) mice infected with mouse hepatitis virus (JHM strain, JHMV) develop severe encephalitis, with death occurring within 7 days. Here, we show that the host response to a single JHMV-specific immunodominant CD4 T-cell epitope is critical for severe disease. We engineered a recombinant JHMV with mutations in the immunodominant CD4 T-cell epitope (rJ.M(Y135Q)). Infection of naïve B6 mice with this virus resulted in mild disease with no mortality. However, introduction of a CD4 T-cell epitope from Listeria monocytogenes into rJ.M(Y135Q) generated a highly virulent virus. The decrease in disease severity was not due to a switch from Th1 to Th2 predominance in rJ.M(Y135Q)-infected mice, an effect on CD8 T-cell function, or differential expression of tumor necrosis factor-alpha by JHMV-specific CD4 T cells. These results show that the response to a single virus-specific CD4 T-cell epitope may contribute to a pathogenic host response in the setting of acute viral disease and that abrogation of this response ameliorates clinical disease without diminishing virus clearance.

Mutation

Immunodominant Epitopes - immunology

Viral Matrix Proteins - genetics

Enzyme-Linked Immunosorbent Assay

Humans

Brain - virology

Epitopes, T-Lymphocyte - genetics

Listeria monocytogenes - immunology

Reverse Transcriptase Polymerase Chain Reaction

Coronaviridae Infections - immunology

CD4-Positive T-Lymphocytes - immunology

Murine hepatitis virus - immunology

Animals

Listeria monocytogenes - genetics

Mice

Mice, Inbred BALB C

Viral Matrix Proteins - immunology

Epitopes, T-Lymphocyte - immunology

HeLa Cells

Immunodominant Epitopes - genetics

CD4-Positive T-Lymphocytes - virology

Brain - immunology

Encephalitis, Viral - immunology

Murine hepatitis virus - genetics

Details

Title: Subtitle: Pathogenic role for virus-specific CD4 T cells in mice with coronavirus-induced acute encephalitis
Creators: Daniela Anghelina - Department of Pediatrics, University of Iowa, Medical Laboratories 2042, Iowa City, IA 52242, USA
Lecia Pewe
Stanley Perlman
Resource Type: Journal article
Publication Details: The American journal of pathology, Vol.169(1), pp.209-222
DOI: 10.2353/ajpath.2006.051308
PMID: 16816374
PMCID: PMC1698761
NLM abbreviation: Am J Pathol
ISSN: 0002-9440
eISSN: 1525-2191
Publisher: United States
Grant note: NS36592 / NINDS NIH HHS R01 NS036592 / NINDS NIH HHS
Language: English
Date published: 07/2006
Academic Unit: Microbiology and Immunology; University of Iowa; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777477202771

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