Antiviral antibodies are necessary to prevent cytotoxic T-lymphocyte escape in mice infected with a coronavirus.
Mutation within virus-derived CD8 T-cell epitopes can effectively abrogate cytotoxic T-lymphocyte (CTL) recognition and impede virus clearance in infected hosts. These so-called "CTL escape variant viruses" are commonly selected during persistent infections and are associated with rapid disease progression and increased disease severity. Herein, we tested whether antiviral antibody-mediated suppression of virus replication and subsequent virus clearance were necessary for preventing CTL escape in coronavirus-infected mice. We found that compared to wild-type mice, B-cell-deficient mice did not efficiently clear infectious virus, uniformly developed clinical disease, and harbored CTL escape variant viruses. These data directly demonstrate a critical role for antiviral antibody in protecting from the selective outgrowth of CTL escape variant viruses.
Butler
Noah S
NS
Program in Immunology, University of Iowa, Iowa City, Iowa 52242, USA.
Dandekar
Ajai A
AA
Perlman
Stanley
S
D000818:Animals; D000833:Animals, Suckling; D000914:Antibodies, Viral / Q000276:immunology*; D018352:Coronavirus Infections / Q000276:immunology / Q000401:mortality* / Q000821:virology; D004679:Encephalomyelitis / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D018984:Epitopes, T-Lymphocyte / Q000235:genetics; D005260:Female; D006801:Humans; D016056:Immunodominant Epitopes / Q000235:genetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D006517:Murine hepatitis virus / Q000235:genetics / Q000276:immunology*; D009154:Mutation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D000914:Antibodies, Viral; D018984:Epitopes, T-Lymphocyte; D016056:Immunodominant Epitopes