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Isolation and characterisation of a defective measles virus from a subacute sclerosing panencephalitis patient
Abstract:
A cytopathic measles virus was isolated from a brain biopsy of a subacute sclerosing panencephalitis (SSPE) patient. The agent could be transferred to Vero cells by cocultivation, but the infectivity always remained cell-associated -ie, a defective virus infection. The cell-associated nature of the virus was retained through 25 passages in Vero cells. Intracerebral inoculation of hamsters (2-6 days old) with the cocultured Vero cells gave rise to 100% mortality in 5-7 days. The virus retained its cell-associated nature after passage in hamsters. Electron microscopy of the brain and Vero cocultures showed the presence of virus-like ribonucleoparticles mainly in the nucleus. The presence of viral antigens in the nucleus, cytoplasm, and on the plasma membranes was confirmed by immunofluorescence. Using a combination of immunological and biochemical techniques, it was shown that all the viral proteins were synthesized with the exception of the haemagglutinin. Inclusion of the fusion inhibitor SV4814 (CBZ-D phenylalanine-L-phenylalanine-L-arginine-NO2) in the culture medium led to the elimination of the SSPE infection.
Insights
A defective measles virus causing subacute sclerosing panencephalitis (SSPE) was isolated. A fusion inhibitor eliminated the SSPE infection in cell cultures, suggesting a potential therapeutic target.
Area of Science:
- Virology
- Neuroscience
- Cell Biology
Background:
- Subacute sclerosing panencephalitis (SSPE) is a rare, fatal neurological complication of measles virus infection.
- The pathogenesis of SSPE involves persistent measles virus infection in the central nervous system.
Purpose of the Study:
- To isolate and characterize the measles virus responsible for SSPE.
- To investigate the nature of the viral infection in SSPE.
- To explore potential therapeutic interventions for SSPE.
Main Methods:
- Isolation of measles virus from SSPE patient brain biopsy.
- Cocultivation of infected cells with Vero cells to assess viral transfer and infectivity.
- Intracerebral inoculation of hamsters to evaluate pathogenicity.
- Electron microscopy for visualization of viral particles.
- Immunofluorescence assays to detect viral antigens.
- Immunological and biochemical techniques to analyze viral protein synthesis.
- Treatment with a fusion inhibitor (SV4814) to assess its effect on infection.
Main Results:
- A cytopathic, cell-associated measles virus was isolated from an SSPE patient.
- The isolated virus caused 100% mortality in young hamsters upon intracerebral inoculation.
- Virus-like ribonucleoparticles were observed in the nucleus of infected cells and hamster brains.
- Viral antigens were detected in various cellular compartments.
- All viral proteins were synthesized except for haemagglutinin.
- The fusion inhibitor SV4814 successfully eliminated the SSPE infection in vitro.
Conclusions:
- The study successfully isolated and characterized a defective measles virus associated with SSPE.
- The cell-associated nature and specific protein synthesis profile of the virus were elucidated.
- The findings highlight the potential of fusion inhibitors as a therapeutic strategy against SSPE.