Infection with cytotoxic T-lymphocyte escape mutants results in increased mortality and growth retardation in mice infected with a neurotropic coronavirus

L Pewe; S Xue; S Perlman

doi:10.1128/JVI.72.7.5912-5918.1998

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Infection with cytotoxic T-lymphocyte escape mutants results in increased mortality and growth retardation in mice infected with a neurotropic coronavirus

Journal article

Open access

Peer reviewed

Infection with cytotoxic T-lymphocyte escape mutants results in increased mortality and growth retardation in mice infected with a neurotropic coronavirus

L Pewe, S Xue and S Perlman

Journal of virology, Vol.72(7), pp.5912-5918

07/1998

DOI: 10.1128/JVI.72.7.5912-5918.1998

PMCID: PMC110395

PMID: 9621053

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https://europepmc.org/articles/pmc110395View

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Abstract

C57BL/6 mice infected with mouse hepatitis virus strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis several weeks after inoculation. Previously, we showed that mutations in the immunodominant CD8 T-cell epitope (S-510-518) could be detected in nearly all samples of RNA and virus isolated from these mice. These mutations abrogated recognition by T cells harvested from the central nervous systems of infected mice in direct ex vivo cytotoxicity assays. These results suggested that cytotoxic T-lymphocyte (CTL) escape mutants contributed to virus amplification and the development of clinical disease in mice infected with wild-type virus. In the present study, the importance of these mutations was further evaluated by infecting naive mice with MHV-JHM variants isolated from infected mice and in which epitope S-510-518 was mutated. Compared to mice infected with wild-type virus, variant virus-infected animals showed higher mortality and morbidity manifested by decreased weight gain and neurological signs. Although a delay in the kinetics of virus clearance has been demonstrated in previous studies of CTL escape mutants, this is the first illustration of significant changes in clinical disease resulting from infection with viruses able to evade the CD8 T-cell immune response.

Murine hepatitis virus - immunology

T-Lymphocytes, Cytotoxic - immunology

Animals

Encephalomyelitis - etiology

Growth Disorders - etiology

Mice

Mice, Inbred BALB C

Epitopes, T-Lymphocyte

Mutation

Coronavirus Infections - mortality

Coronavirus Infections - immunology

Details

Title: Subtitle: Infection with cytotoxic T-lymphocyte escape mutants results in increased mortality and growth retardation in mice infected with a neurotropic coronavirus
Creators: L Pewe - Departments of Pediatrics, University of Iowa, Iowa City, Iowa 52242, USA
S Xue
S Perlman
Resource Type: Journal article
Publication Details: Journal of virology, Vol.72(7), pp.5912-5918
DOI: 10.1128/JVI.72.7.5912-5918.1998
PMID: 9621053
PMCID: PMC110395
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Grant note: NS 36592 / NINDS NIH HHS R01 NS036592 / NINDS NIH HHS
Language: English
Date published: 07/1998
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777354502771

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