Cytotoxic T cell-resistant variants are selected in a virus-induced demyelinating disease.
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.
Pewe
L
L
Department of Pediatrics, University of Iowa, Iowa City 52242, USA.
Wu
G F
GF
Barnett
E M
EM
Castro
R F
RF
Perlman
S
S
D000818:Animals; D001483:Base Sequence; D018352:Coronavirus Infections / Q000209:etiology*; D003602:Cytotoxicity, Immunologic; D003711:Demyelinating Diseases / Q000209:etiology*; D000939:Epitopes / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D006517:Murine hepatitis virus; D009154:Mutation; D012367:RNA, Viral / Q000032:analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000939:Epitopes; D012367:RNA, Viral