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Characterization of the Hallé SSPE measles virus isolate
Abstract:
The Hallé subacute sclerosing panencephalitis (SSPE) measles virus isolate and its plaque-purified progeny were investigated to determine whether any unusual properties could be associated with its ability to cause persistent infection. Three types of plaque-purified progeny were isolated. One population appeared to be similar in biological and biochemical properties to laboratory-adapted measles virus and had the ability to induce syncytia (syn+). A second population (syn-) plaqued more efficiently at 39 degrees C than at 33 degrees C, did not cause normal cell fusion at either temperature, and produced particles that interfered with the replication of other measles virus isolates in vivo and in vitro. This syn- virus was further plaque-purified to eliminate the interfering particles, producing the syn- P2 virus. This virus also plaqued more efficiently at 39 degrees C than at 33 degrees C, but caused cell fusion only at 39 degrees C. Both syn- viruses and the parental virus were significantly less virulent in vivo than the syn+ virus and caused a more prolonged infection. Biochemical analysis showed that the syn- P2 population produced particles that banded at two different densities in potassium tartrate gradients; both densities were less than those of the standard laboratory measles virus and the syn+ virus. Although the syn- P2 virus did not cause cell fusion at 33 degrees C, [35S]methionine labelling demonstrated that the haemolysin/cell fusion protein was present in syn- P2 virions. The production of interfering particles, the inability to cause cell fusion at 33 degrees C, and the cold-sensitive nature of the syn- population appear to play a role in the ability of the Hallé SSPE virus to establish persistent infection.
Insights
Investigating the Hallé subacute sclerosing panencephalitis (SSPE) measles virus revealed distinct progeny strains. Cold-sensitive, non-syncytial measles virus variants with interfering particles contribute to persistent SSPE infections.
Area of Science:
- Virology
- Neuroscience
- Infectious Diseases
Background:
- Subacute sclerosing panencephalitis (SSPE) is a rare, persistent measles virus infection of the central nervous system.
- The Hallé SSPE measles virus isolate exhibits unique properties potentially linked to its persistent nature.
Purpose of the Study:
- To investigate the biological and biochemical properties of the Hallé SSPE measles virus and its plaque-purified progeny.
- To determine the characteristics associated with the virus's ability to establish persistent infections.
Main Methods:
- Plaque purification of measles virus progeny.
- Characterization of syncytia (cell fusion) induction at different temperatures.
- In vivo and in vitro replication interference assays.
- Biochemical analysis of viral particle density and protein expression.
Main Results:
- Three distinct progeny populations were isolated: syn+ (similar to lab virus), syn- (thermosensitive, interfering), and syn- P2 (further purified syn-).
- Syn- variants were less virulent, caused prolonged infections, and produced lower-density viral particles compared to syn+.
- Syn- P2 showed temperature-dependent cell fusion and contained the fusion protein, despite reduced fusion at 33°C.
Conclusions:
- The production of interfering particles and temperature-sensitive cell fusion are key factors in the Hallé SSPE measles virus's persistent infection capability.
- These properties, particularly the cold-sensitive nature of syn- variants, likely contribute to the pathogenesis of SSPE.