Cytotoxic T-cell-resistant variants arise at early times after infection in C57BL/6 but not in SCID mice infected with a neurotropic coronavirus

L Pewe; S Xue; S Perlman

doi:10.1128/JVI.71.10.7640-7647.1997

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Cytotoxic T-cell-resistant variants arise at early times after infection in C57BL/6 but not in SCID mice infected with a neurotropic coronavirus

Journal article

Open access

Peer reviewed

Cytotoxic T-cell-resistant variants arise at early times after infection in C57BL/6 but not in SCID mice infected with a neurotropic coronavirus

L Pewe, S Xue and S Perlman

Journal of virology, Vol.71(10), pp.7640-7647

10/1997

DOI: 10.1128/JVI.71.10.7640-7647.1997

PMCID: PMC192113

PMID: 9311846

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Abstract

Under certain conditions, C57BL/6 mice persistently infected with mouse hepatitis virus strain JHM (MHV-JHM) develop clinical disease and histological evidence of demyelination several weeks after inoculation with virus. In a previous report, we showed that mutations in the RNA encoding an immunodominant CD8 T-cell epitope within the surface glycoprotein (epitope S-510-518) were present in all persistently infected animals and that these mutations abrogated recognition by virus-specific cytotoxic T cells (CTLs) in direct ex vivo cytotoxicity assays. To obtain further evidence that these mutations were necessary for the development of clinical disease, the temporal course of their appearance was determined. Mutations in the epitope were identified by 10 to 12 days after inoculation, and in some mice, virus containing mutated epitope was the dominant species detected by 15 days. In addition, most mice that remain asymptomatic at 80 days after inoculation, a time after which clinical disease almost never develops, were infected with only wild-type virus. Finally, analysis of virus isolated from mice with severe combined immunodeficiency (SCID) revealed the presence only of wild-type epitope S-510-518. These results, by showing that mutations are not selected in SCID mice and occur at early times after inoculation in C57BL/6 mice, support the view that they result from immune pressure and contribute to virus persistence and demyelination in mice infected persistently with MHV-JHM.

Mutation

T-Lymphocytes, Cytotoxic - immunology

Amino Acid Sequence

Sequence Deletion

Species Specificity

Mice, Inbred C57BL

Brain - virology

Coronavirus Infections - physiopathology

RNA, Viral - analysis

Mice, SCID

Coronavirus Infections - immunology

Murine hepatitis virus - isolation & purification

Genetic Variation

Murine hepatitis virus - immunology

Point Mutation

Animals

Time Factors

Mice

Spinal Cord - virology

CD8-Positive T-Lymphocytes - immunology

Murine hepatitis virus - genetics

Details

Title: Subtitle: Cytotoxic T-cell-resistant variants arise at early times after infection in C57BL/6 but not in SCID mice infected with a neurotropic coronavirus
Creators: L Pewe - Department of Pediatrics, University of Iowa, Iowa City 52242, USA
S Xue
S Perlman
Resource Type: Journal article
Publication Details: Journal of virology, Vol.71(10), pp.7640-7647
DOI: 10.1128/JVI.71.10.7640-7647.1997
PMID: 9311846
PMCID: PMC192113
NLM abbreviation: J Virol
ISSN: 0022-538X
eISSN: 1098-5514
Publisher: United States
Language: English
Date published: 10/1997
Academic Unit: Microbiology and Immunology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Infectious Disease (Pediatrics)
Record Identifier: 9983777350602771

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