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Pathogenesis of murine encephalitis limited by defective interfering particles. An immunohistochemical study
I V Plakhov1, C Aoki, C S Reiss
1Department of Biology, New York University, NY 10003-6688, USA.
Abstract:
To determine whether defective interfering (DI) particles alter viral encephalitis BALB/c mice were inoculated intranasally with standard vesicular stomatitis virus (VSV) and its DI particles. Addition of 10(7) PFU equivalents of DI particles to 10(5) PFU of VSV reduced morbidity but did not delay disease onset. Less mortality was also observed. When 10(3) PFU equivalents of DI particles or UV-irradiated DI particles were substituted, these effects were absent. Attempts to correlate mortality with virus recovered from the brain could not be made due to considerable variations in the few surviving mice. Immunohistochemical analysis obtained from 121 mice showed that inoculation of DI particles limited the specific pathways of VSV antigen dissemination within the central nervous system, and new pathways were not substituted. In the group of mice with reduced mortality due to DI particles, at day 4 post inoculation VSV antigen was limited to the outer layers of the glomeruli of the olfactory bulb and to the accessory olfactory bulb, whereas there was deeper invasion of the olfactory bulb and olfactory ventricular system with mice infected with standard VSV alone. Correlation between mortality and extent of invasion became more difficult to make from 8 days on, when VSV antigens were found in discrete areas of the brain. By 12 days, few surviving mice contained any detectable VSV antigen in their brains. These results demonstrate that DI particles have potential as therapeutic agents. Also, mortality resulting from VSV-induced encephalitis, although poorly understood, may be determined very early, possibly while the virus is replicating at the site of inoculation.
Insights
Defective interfering (DI) particles reduced mortality and morbidity in vesicular stomatitis virus (VSV)-induced encephalitis in mice. DI particles limited viral spread in the central nervous system, showing therapeutic potential.
Area of Science:
- Virology
- Immunology
- Neuroscience
Background:
- Viral encephalitis poses a significant health threat.
- Vesicular stomatitis virus (VSV) is a model pathogen for studying encephalitis.
- Defective interfering (DI) particles are variants of viruses that can interfere with standard virus replication.
Purpose of the Study:
- To investigate the effect of DI particles on VSV-induced viral encephalitis in BALB/c mice.
- To determine if DI particles can alter disease progression and mortality.
- To analyze the dissemination pathways of VSV antigen within the central nervous system (CNS) in the presence of DI particles.
Main Methods:
- BALB/c mice were intranasally inoculated with standard VSV and its DI particles.
- Morbidity and mortality were monitored.
- Immunohistochemical analysis was performed on brain tissue from 121 mice to track VSV antigen dissemination.
- Different concentrations and UV-irradiated DI particles were tested.
Main Results:
- Addition of high-dose DI particles (10^7 PFU equivalents) to VSV (10^5 PFU) reduced morbidity and mortality but did not delay disease onset.
- Lower doses or UV-irradiated DI particles did not show these protective effects.
- Immunohistochemistry revealed that DI particles limited VSV antigen dissemination pathways within the CNS.
- At day 4 post-inoculation, VSV antigen was restricted to outer layers of the olfactory bulb in mice treated with DI particles, unlike deeper invasion in controls.
Conclusions:
- DI particles demonstrate potential as therapeutic agents against VSV-induced encephalitis.
- The early stages of viral replication at the inoculation site may be critical in determining mortality.
- DI particles modulate the host's immune response by limiting viral spread within the CNS.