Related Experiment Videos
Theiler's murine encephalomyelitis virus kills restrictive but not permissive cells by apoptosis
1Division of Neurology, Evanston Hospital, Illinois 60201, USA.
Abstract:
Theiler's murine encephalomyelitis viruses (TMEV), genus Cardiovirus, family Picorniviridae, are natural enteric pathogens of mice which cause central nervous system demyelination similar to that seen in multiple sclerosis. TMEV can be classified into two groups based on neurovirulence: a highly virulent group, e.g., GDVII virus, and a less virulent group, e.g., BeAn virus. Both viruses, depending on the multiplicity of infection, produced cytopathology in BSC-1 cells similar to that in BHK-21 cells. Since apoptosis has been reported as a mechanism of cell death after infection with many viruses, we examined infected BHK-21 and BSC-1 cells for morphological and biochemical changes consistent with apoptosis. Only the restrictive BSC-1 cells showed evidence of nuclear morphology and internucleosomal DNA degradation indicative of apoptosis. Interestingly, the more virulent GDVII virus was at least 50-fold more efficient in inducing apoptosis than the less virulent BeAn virus. This difference was not due to greater GDVII viral RNA replication or production of infectious virus, since the two viruses were similarly restricted in BSC-1 cells. Apoptosis in BSC-1 cells appears to be triggered by a cytoplasmic event, since inactivation of GDVII viral RNA by UV light abolished the ability of the virus to induce apoptosis. The possible role of apoptosis in the pathogenesis of TMEV infection in mice, especially virus persistence in central nervous system macrophages, is discussed.
Insights
Theiler's murine encephalomyelitis viruses (TMEV) induce apoptosis in mouse cells, with more virulent strains causing greater cell death. This programmed cell death may play a role in TMEV pathogenesis and persistence in the central nervous system.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Theiler's murine encephalomyelitis viruses (TMEV) are enteric pathogens causing central nervous system demyelination, mimicking multiple sclerosis.
- TMEV strains vary in neurovirulence, with GDVII being highly virulent and BeAn less virulent.
Purpose of the Study:
- To investigate the role of apoptosis (programmed cell death) in TMEV-induced cytopathology.
- To compare the apoptotic potential of virulent (GDVII) and less virulent (BeAn) TMEV strains in cell culture.
Main Methods:
- Infection of BHK-21 and BSC-1 cells with TMEV strains.
- Assessment of morphological and biochemical markers of apoptosis, including nuclear morphology and DNA degradation.
- Evaluation of viral RNA replication and infectious virus production.
- UV inactivation of viral RNA to assess the trigger for apoptosis.
Main Results:
- Apoptosis was observed in restrictive BSC-1 cells, characterized by nuclear changes and DNA fragmentation.
- The highly virulent GDVII virus induced apoptosis approximately 50-fold more efficiently than the less virulent BeAn virus.
- Apoptosis induction correlated with viral RNA presence, not viral replication or infectious virus yield, suggesting a cytoplasmic trigger.
Conclusions:
- Apoptosis is a mechanism of cell death induced by TMEV in susceptible cells.
- Viral virulence correlates with the capacity to induce apoptosis, independent of replication efficiency.
- Cytoplasmic events triggered by viral RNA likely initiate apoptosis, potentially influencing TMEV pathogenesis and persistence in the central nervous system.