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Absence of M protein in a cell-associated subacute sclerosing panencephalitis virus
Abstract:
Measles virus has been suggested to cause subacute sclerosing panencephalitis (SSPE), a slow central nervous system disease of children. However, several questions remain about the pathogenesis of SSPE. For example, it is not known whether alteration of the measles virus genome has a role in the initiation and persistence of the disease. Several studies have compared the RNA and protein composition of wild-type (wt) and SSPE strains of measles virus in a search for markers characteristic of the latter. All the studies used SSPE strains that had reverted to the budding, virion-producing form, similar to wt. We have shown, however, that only cell-associated non-budding strains of SSPE virus cause an SSPE-like persistent infection in young ferrets. Strong cell association and cell-fusing activity were essential for the virulence of measles virus in the brains of experimental animals and possibly humans. We have, therefore, compared the protein composition of virulent SSPE strains to that of the budding, non-virulent SSPE and wt strains. We report here that the M protein was not detectable in non-budding SSPE strains D.R., Biken and IP-3, and strain D.R. contained very little H protein.
Insights
Measles virus strains causing persistent infections and subacute sclerosing panencephalitis (SSPE) lack M protein. This finding is crucial for understanding SSPE pathogenesis and developing targeted therapies.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Subacute sclerosing panencephalitis (SSPE) is a slow central nervous system disease linked to measles virus.
- The exact role of measles virus genome alterations in SSPE initiation and persistence remains unclear.
- Previous studies compared wild-type and SSPE measles virus strains, but used only virion-producing SSPE strains.
Purpose of the Study:
- To investigate the role of measles virus protein composition in SSPE pathogenesis.
- To compare protein profiles of virulent, cell-associated SSPE strains with non-virulent, budding strains.
- To identify potential viral markers associated with SSPE-like persistent infections.
Main Methods:
- Comparison of protein composition between different measles virus strains (wild-type, budding SSPE, non-budding SSPE).
- Analysis of viral protein expression, specifically M and H proteins.
- Utilizing a ferret model to assess SSPE-like persistent infections.
Main Results:
- Only cell-associated, non-budding SSPE virus strains induced SSPE-like persistent infections in ferrets.
- The M protein was undetectable in non-budding SSPE strains (D.R., Biken, IP-3).
- Strain D.R. showed significantly reduced levels of the H protein.
Conclusions:
- The absence of M protein is a characteristic of non-budding SSPE virus strains.
- Strong cell association and cell-fusing activity are critical for measles virus virulence in the central nervous system.
- These viral protein alterations may play a key role in SSPE pathogenesis.