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Cytotoxic T cell-resistant variants are selected in a virus-induced demyelinating disease
Journal article   Open access   Peer reviewed

Cytotoxic T cell-resistant variants are selected in a virus-induced demyelinating disease

L Pewe, G F Wu, E M Barnett, R F Castro and S Perlman
Immunity, Vol.5(3), pp.253-262
09/1996
DOI: 10.1016/S1074-7613(00)80320-9
PMID: 8808680
url
https://doi.org/10.1016/S1074-7613(00)80320-9View
Published (Version of record) Open Access

Abstract

C57BI/6 mice infected with mouse hepatitis virus, strain JHM (MHV-JHM) develop a chronic demyelinating encephalomyelitis. Infectious virus can be isolated only from symptomatic mice. In C57BI/6 mice, two CD8+ T cell epitopes within the MHV-JHM surface glycoprotein were previously identified. Here, we show that mutations in the RNA encoding the immunodominant of the epitopes are present in nearly all virus samples isolated from these mice. Mutations are not present in sequences flanking this epitope or in other CD8+ or CD4+ T cell epitopes. Furthermore, analysis of five peptides corresponding to variant epitopes in direct ex vivo cytotoxicity assays showed that each mutation caused a loss of epitope recognition. These results suggest that escape from CD8+ T cell recognition is necessary for enhanced virus replication and development of clinical disease in these MHV-JHM-infected mice.
Mutation T-Lymphocytes, Cytotoxic - immunology Mice, Inbred C57BL Molecular Sequence Data RNA, Viral - analysis Epitopes - genetics Murine hepatitis virus Animals Base Sequence Demyelinating Diseases - etiology Mice Coronavirus Infections - etiology Cytotoxicity, Immunologic

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