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Persistence of virulent Semliki Forest virus in mouse brain following co-inoculation with defective interfering
Abstract:
Semliki Forest virus (SFV) normally causes an acute lethal encephalitis in mice following intranasal inoculation. However, animals co-administered with 10 LD50 SFV and defective interfering (DI) SFV survive the infection without clinical signs of disease. In this report we demonstrate the isolation of infectious virus from the brains of 12/169 protected mice up to 6.5 months post-infection. Although, with one exception, mice were clinically normal, five of 12 of the SFV isolates were identical to the original virus as judged by plaque morphology, maximum temperature for growth, virulence in mice and pathology. Others were less virulent (although not any were plaque or temperature-sensitive mutants) and on re-inoculation into fresh mice caused a demyelinating pathology which was not an attribute of the original inoculum. How the virulent virus can persist in brain, sometimes in amounts in excess of 100 LD50, without causing disease remains to be determined.
Insights
Semliki Forest virus (SFV) can persist in mouse brains long-term after co-administration with defective interfering (DI) SFV. Some persistent SFV strains remained virulent, while others caused novel demyelinating pathology.
Area of Science:
- Virology
- Neuroscience
- Immunology
Background:
- Semliki Forest virus (SFV) typically induces lethal encephalitis in mice.
- Co-administration with defective interfering (DI) SFV confers protection against SFV-induced disease.
Purpose of the Study:
- To investigate the persistence of infectious SFV in the brains of protected mice.
- To characterize the properties of SFV isolates recovered from protected mice.
Main Methods:
- Intranasal inoculation of mice with SFV and DI SFV.
- Isolation and characterization of SFV from mouse brains up to 6.5 months post-infection.
- Assessment of viral plaque morphology, growth temperature, virulence, and pathology.
Main Results:
- Infectious SFV was isolated from 12 out of 169 protected mice.
- Five of the 12 SFV isolates were identical to the original virulent virus.
- Other isolates exhibited reduced virulence and induced demyelinating pathology upon re-inoculation.
Conclusions:
- Virulent SFV can persist in the brain for extended periods without causing overt clinical signs.
- Persistent SFV strains can either retain their original virulence or evolve to cause distinct neuropathologies.
- The mechanisms underlying SFV persistence and the emergence of novel pathologies require further investigation.