Affiliation:
1. Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-6076
Abstract
ABSTRACT
Both CD4
+
and CD8
+
T cells are required for clearance of the murine coronavirus mouse hepatitis virus (MHV) during acute infection. We investigated the effects of an epitope-specific CD8
+
T-cell response on acute infection of MHV, strain A59, in the murine CNS. Mice with CD8
+
T cells specific for gp33-41 (an H-2D
b
-restricted CD8
+
T-cell epitope derived from lymphocytic choriomeningitis glycoprotein) were infected with a recombinant MHV-A59, also expressing gp33-41, as a fusion protein with enhanced green fluorescent protein (EGFP). By 5 days postinfection, these mice showed significantly (approximately 20-fold) lower titers of infectious virus in the brain compared to control mice. Furthermore mice with gp33-41-specific CD8
+
cells exhibited much reduced levels of viral antigen in the brain as measured by immunohistochemistry using an antibody directed against viral nucleocapsid. More than 90% of the viruses recovered from brain lysates of such protected mice, at 5 days postinfection, had lost the ability to express EGFP and had deletions in their genomes encompassing EGFP and gp33-41. In addition, genomes of viruses from about half the plaques that retained the EGFP gene had mutations within the gp33-41 epitope. On the other hand, gp33-41-specific cells failed to protect perforin-deficient mice from infection by the recombinant MHV expressing gp33, indicating that perforin-mediated mechanisms were needed. Virus recovered from perforin-deficient mice did not exhibit loss of EGFP expression and the gp33-41 epitope. These observations suggest that the cytotoxic T-cell response to gp33-41 exerts a strong immune pressure that quickly selects epitope escape mutants to gp33-41.
Publisher
American Society for Microbiology
Subject
Virology,Insect Science,Immunology,Microbiology
Reference40 articles.
1. Bergmann, C. C., B. Parra, D. R. Hinton, R. Chandran, M. Morrison, and S. A. Stohlman. 2003. Perforin-mediated effector function within the central nervous system requires IFN-gamma-mediated MHC up-regulation. J. Immunol.170:3204-3213.
2. CD8+ T-cell epitopes within the surface glycoprotein of a neurotropic coronavirus and correlation with pathogenicity
3. Castro, R. F., and S. Perlman. 1996. Differential antigen recognition by T cells from the spleen and central nervous system of coronavirus-infected mice. Virology222:247-251.
4. Cormack, B. P., R. H. Valdivia, and S. Falkow. 1996. FACS-optimized mutants of the green fluorescent protein (GFP). Gene173:33-38.
5. Das Sarma, J., E. Scheen, S. Seo, M. Koval, and S. R. Weiss. 2002. Enhanced green fluorescent protein expression may be used to monitor murine coronavirus spread in vitro and in the mouse central nervous system. J. Neurovirol.8:1-11.
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