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Central nervous system immunity in mice infected with theiler's virus. I. Local neutralizing antibody response
Abstract:
Experimental Theiler's mouse encephalomyelitis virus (TMEV) infection in mice is atypical of most other picornavirus infections because virus persists in the host. It was shown previously that low levels of infectious virus are readily detectable in the central nervous system (CNS) despite the presence of substantial titers of serum neutralizing antibody. In this study antibody assays were performed on CNS tissue homogenates, and neutralizing antibody was regularly found in the CNS of TMEV-infected mice. That neutralization by infected CNS extracts was due to antibody was demonstrated by the specificity of neutralization for TMEV and by elimination or marked reduction of neutralization by in vitro treatment with goat antiserum to mouse IgG. In addition, immunofluorescent staining consistently revealed IgG- but not IgM-containing cells in perivascular cuffs and parenchymal lesions of the brains of infected animals. Evidence of local antibody formation in the CNS was found in the actual reversal of the serum-CNS antibody ratio in about one-third of infected mice after three weeks. In contrast, normal mice had a mean serum-CNS antibody ratio of approximately 100:1 after passive transfer of antibody. Possible reasons for the fact that TMEV is not neutralized by antibody and chronic infection is not aborted include the formation of complexes of infectious virus and antibody in the CNS and the production of antibodies with low affinity for TMEV.
Insights
Theiler
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Theiler's mouse encephalomyelitis virus (TMEV) infection in mice typically results in persistent viral presence, unlike most picornavirus infections.
- Infectious TMEV is detectable in the central nervous system (CNS) even with high serum neutralizing antibody titers.
- This persistence raises questions about the efficacy of the immune response in the CNS.
Purpose of the Study:
- To investigate the presence and role of neutralizing antibodies within the CNS during TMEV infection.
- To explore potential mechanisms by which TMEV evades neutralization and establishes chronic infection in the CNS.
Main Methods:
- Antibody assays were conducted on CNS tissue homogenates from TMEV-infected mice.
- Neutralization activity was confirmed using TMEV-specific assays and goat antiserum to mouse IgG.
- Immunofluorescent staining identified IgG- and IgM-containing cells in brain lesions.
- Serum-CNS antibody ratios were analyzed and compared to passive transfer controls.
Main Results:
- Neutralizing antibody was consistently detected in the CNS of TMEV-infected mice.
- Evidence of local antibody production within the CNS was observed, with reversed serum-CNS antibody ratios in some mice.
- Immunofluorescence revealed IgG-containing cells in CNS lesions, indicating local antibody synthesis.
Conclusions:
- The CNS is a site of antibody production during TMEV infection.
- Chronic TMEV infection may persist due to the formation of infectious virus-antibody complexes in the CNS or the generation of low-affinity antibodies.