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Molecular mechanism for retroviral neuropathogenesis: possible involvement of capillary endothelial cells
M Masuda1, M Masuda, S K Ruscetti
1Laboratory of Molecular Oncology, National Cancer Institute, Frederick, Maryland 21702, USA.
Abstract:
A neuropathogenic variant of Friend MuLV, PVC-211, causes rapidly progressive spongiform neurodegeneration in susceptible rats and mice. Major targets of PVC-211 MuLV infection are brain capillary endothelial cells (BCEC), suggesting that virus-infected BCEC may play crucial roles in neurological disease induction. Consistent with this possibility, studies using chimeric viruses constructed between PVC-211 MuLV and non-neuropathogenic Friend MuLV have revealed that the BCEC tropism of the virus correlates with its neuropathogenicity. Possible involvement of cytokine expression by PVC-211 MuLV-infected BCEC in the induction of neuropathological changes will be discussed.
Insights
A specific strain of Friend Murine Leukemia Virus (MuLV), PVC-211, causes spongiform neurodegeneration by infecting brain capillary endothelial cells (BCEC). Virus targeting of BCEC correlates with disease severity, suggesting BCEC
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Friend MuLV is a retrovirus known to cause disease in rodents.
- A specific variant, PVC-211, induces spongiform neurodegeneration.
- Brain capillary endothelial cells (BCEC) are identified as primary targets of PVC-211 MuLV.
Purpose of the Study:
- To investigate the role of BCEC tropism in PVC-211 MuLV neuropathogenicity.
- To explore the mechanisms by which PVC-211 MuLV infection leads to neurodegeneration.
Main Methods:
- Construction and analysis of chimeric viruses between PVC-211 MuLV and non-neuropathogenic Friend MuLV.
- Assessment of viral tropism and neuropathological changes in infected rodents.
Main Results:
- The tropism of PVC-211 MuLV for BCEC was found to correlate directly with its neuropathogenic potential.
- Infection of BCEC by PVC-211 MuLV is a key factor in inducing spongiform neurodegeneration.
Conclusions:
- PVC-211 MuLV infects BCEC, which is critical for causing spongiform neurodegeneration.
- The tropism of the virus for these cells dictates its neuropathogenicity.
- Cytokine expression by infected BCEC may contribute to neuropathological changes.