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Theiler's virus-associated antigens on the surfaces of cultured glial cells
M Rodriguez1, L M Siegel, D Hovanec-Burns
1Department of Neurology, Mayo Clinic, Rochester, Minnesota 55905.
Abstract:
Infection of the central nervous system by Theiler's murine encephalomyelitis virus (TMEV), a picornavirus, produces chronic demyelinating disease in susceptible mice. In this immunoelectron microscopic study of TMEV infection of neonatal mouse brain cells in culture, TMEV antigen was found on the surfaces of infected oligodendrocytes and astrocytes by labeling with hyperimmune serum from TMEV-infected mice or with rabbit antiserum to purified inactivated DA strain TMEV. Brain-derived macrophages had no TMEV-specific antigen on their surfaces and were not able to maintain productive TMEV infection, even though TMEV antigen was present in the cytoplasm. The presence of TMEV antigens on the surfaces of oligodendrocytes (myelin-producing cells) was unexpected because picornaviruses are nonenveloped viruses and do not bud from cell surfaces. The finding is consistent with the hypothesis that demyelination follows damage of infected oligodendrocytes by immune cells or immunoglobulins that recognize surface virus antigen.
Insights
Theiler
Area of Science:
- Neurovirology
- Immunology
- Cell Biology
Background:
- Theiler's murine encephalomyelitis virus (TMEV) causes chronic demyelinating disease in mice.
- Understanding TMEV's interaction with central nervous system (CNS) cells is crucial for studying demyelination.
Purpose of the Study:
- To investigate the presence and location of TMEV antigens on infected neonatal mouse brain cells in culture.
- To explore the implications of antigen localization for TMEV pathogenesis and demyelination.
Main Methods:
- Immunoelectron microscopy was used to detect TMEV antigens.
- Labeling was performed using hyperimmune serum from TMEV-infected mice and rabbit antiserum to inactivated TMEV.
- Infection and antigen presence were assessed in oligodendrocytes, astrocytes, and macrophages.
Main Results:
- TMEV antigen was detected on the surfaces of infected oligodendrocytes and astrocytes.
- Brain-derived macrophages showed no surface TMEV antigen and limited productive infection.
- Unexpected surface antigen presence on oligodendrocytes (myelin-producing cells) was observed.
Conclusions:
- The presence of TMEV surface antigens on oligodendrocytes supports a hypothesis of immune-mediated demyelination.
- Immune cells or immunoglobulins recognizing surface viral antigens may damage infected oligodendrocytes, leading to demyelination.
- This finding offers insights into the mechanisms of viral-induced CNS damage and autoimmune responses.