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Antiviral Antibodies Are Necessary To Prevent Cytotoxic T-Lymphocyte Escape in Mice Infected with a Coronavirus

Noah S. Butler,¹ Ajai A. Dandekar,^1, and Stanley Perlman^1,2*

Program in Immunology,¹ Department of Microbiology, University of Iowa; Iowa City, Iowa 52242²

Received 19 July 2007/ Accepted 25 September 2007

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.

Published ahead of print on 3 October 2007.

Present address: Department of Internal Medicine, University of Washington, Seattle, WA 98195.