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Journal of Virology, November 2003, p. 11867-11874, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.11867-11874.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Antibody-Mediated Protection against Cytotoxic T-Cell Escape in Coronavirus-Induced Demyelination

Ajai A. Dandekar,1 Gary Jacobsen,2 Thomas J. Waldschmidt,1,3 and Stanley Perlman1,2,4*

Interdisciplinary Program in Immunology,1 Departments of Pediatrics,2 Pathology,3 Microbiology, University of Iowa, Iowa City, Iowa 522424

Received 5 May 2003/ Accepted 5 August 2003

C57BL/6 (B6) mice infected with mouse hepatitis virus (MHV) strain JHM develop a clinically evident, demyelinating encephalomyelitis. Infectious virus can be isolated from the spinal cords of these mice and is invariably mutated in the immunodominant CD8 T-cell epitope recognized in this strain. We showed previously that these persistently infected mice did not mount a measurable serum anti-MHV neutralizing antibody response. Here we show that cytotoxic T-lymphocyte (CTL) escape was not detected in MHV-infected BALB/b mice (H-2b haplotype), even though the same CD8 T-cell epitopes were recognized as in B6 mice. BALB/b mice had 25-fold more MHV-specific antibody-secreting cells in the central nervous system, the site of infection, than B6 mice, suggesting that local production of anti-MHV antibody contributed to this absence of CTL escape. Additionally, administration of anti-MHV neutralizing antibody to infected B6 mice suppressed the development of CTL escape mutants. These findings indicate a key role for the anti-MHV antibody response in suppressing virus replication, thereby minimizing the emergence and competitive advantage of CTL escape mutants.

* Corresponding author. Mailing address: Department of Pediatrics, University of Iowa, 2042 Medical Laboratories, Iowa City, IA 52242. Phone: (319) 335-8549. Fax: (319) 335-8991. E-mail: Stanley-Perlman{at}uiowa.edu.

Journal of Virology, November 2003, p. 11867-11874, Vol. 77, No. 22
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.22.11867-11874.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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