Antibody-mediated protection against cytotoxic T-cell escape in coronavirus-induced demyelination

J Virol. 2003 Nov;77(22):11867-74. doi: 10.1128/jvi.77.22.11867-11874.2003.

Abstract

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-2(b) 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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibodies, Viral / immunology*
  • Antibody-Producing Cells / physiology
  • B-Lymphocytes / immunology
  • Brain / immunology
  • Demyelinating Diseases / immunology*
  • Immunization, Passive
  • Mice
  • Mice, Inbred BALB C
  • Murine hepatitis virus
  • Spleen / immunology
  • T-Lymphocytes, Cytotoxic / immunology*

Substances

  • Antibodies, Viral