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Apoptosis in measles virus-infected human central nervous system tissues
Abstract:
The extent of apoptotic cell death was examined in central nervous system (CNS) tissues from three cases of subacute sclerosing panencephalitis (SSPE). Apoptosis was demonstrated by in situ end-labelling of DNA in formalin-fixed, paraffin-embedded tissue sections. Measles virus and cell types were labelled by immunohistochemistry and/or in situ hybridization. Furthermore, bcl-2 expression in SSPE was examined by immunohistochemistry. All three cases exhibited varying degrees of apoptosis in all CNS areas studied. Brain tissue from a non-neurological control case did not show any significant apoptosis. Characterization of cell types demonstrated neurons, oligodendrocytes, lymphocytes and microglia undergoing apoptosis. A linear relationship could not be established between virus burden and the extent of apoptosis in any particular area. Virus-negative cells were observed which were undergoing apoptosis. Bcl-2 immunoreactivity in SSPE was confined to the infiltrating cell population. These results suggest that apoptosis of various cell types may contribute to the neuropathogenesis of measles virus infection in the human CNS, either as a direct effect of viral infection or by cytokine-mediated responses.
Insights
Subacute sclerosing panencephalitis (SSPE) involves significant apoptotic cell death in the central nervous system (CNS). This programmed cell death affects various brain cells, contributing to SSPE neuropathogenesis.
Area of Science:
- Neuropathology
- Virology
- Immunology
Background:
- Subacute sclerosing panencephalitis (SSPE) is a severe, chronic complication of measles virus infection.
- Understanding the mechanisms of neuronal damage in SSPE is crucial for therapeutic development.
Purpose of the Study:
- To investigate the extent and characteristics of apoptotic cell death in SSPE central nervous system (CNS) tissues.
- To explore the relationship between measles virus presence, cell types undergoing apoptosis, and bcl-2 expression in SSPE.
Main Methods:
- In situ end-labeling of DNA was used to detect apoptosis in formalin-fixed, paraffin-embedded CNS tissues.
- Immunohistochemistry and in situ hybridization were employed to identify measles virus and various cell types.
- Bcl-2 expression was assessed using immunohistochemistry.
Main Results:
- All three SSPE cases showed significant apoptosis across studied CNS areas, unlike control brain tissue.
- Neurons, oligodendrocytes, lymphocytes, and microglia were identified as undergoing apoptosis.
- Apoptosis occurred in both virus-positive and virus-negative cells, with no clear correlation between virus burden and apoptosis extent.
- Bcl-2 immunoreactivity was primarily observed in infiltrating cells.
Conclusions:
- Apoptosis of diverse CNS cell types is a prominent feature in SSPE.
- Programmed cell death may be a key factor in the neuropathogenesis of measles virus infection in the human CNS.
- Apoptosis could be triggered by direct viral effects or cytokine-mediated responses.