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Long-term effects of Semliki Forest virus infection in the mouse central nervous system
S M Donnelly1, B J Sheahan, G J Atkins
1Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland.
Abstract:
Semliki Forest virus (SFV) infection of mice is used as a model to study pathogenic processes occurring in viral encephalitis and demyelinating disease. In this study, the long-term effects of infection by the avirulent M9 mutant of SPV on the central nervous system (CNS) of BALB/c and SJL mice were determined. The presence of infectious virus, viral RNA and cytokine mRNA in the brains of individual mice and the presence of lesions in the spinal cords of the same mice up to 360 days post-infection (d.p.i.) were analysed in order to detect any correlation between these parameters of pathogenesis. Infectious virus could not be detected beyond 7 d.p.i. for either mouse strain. Reverse transcriptase polymerase chain reaction (RT-PCR) was used to detect the presence of the E2 and nsP1 regions of the virus genome and mRNA for interferon-gamma and tumour necrosis factor-alpha. Viral RNA could be detected up to 90 d.p.i. for both mouse strains. Cytokine mRNA could be detected up to 28 d.p.i. for BALB/c mice but up to 360 d.p.i. for SJL mice. Inflammatory lesions, which were associated with cytokine mRNA expression, were not detected in BALB/c mice beyond 28 d.p.i. but were detected in two SJL mice at 90 d.p.i. It is concluded that M9-SFV infection induces long-term prolonged expression of pro-inflammatory cytokines in the CNS of the majority of SJL (but not BALB/c) mice which is not associated with persistence of the virus genome. M9-SFV infection of SJL mice may be a relevant model for the pathogenesis of multiple sclerosis in man.
Insights
Semliki Forest virus (SFV) infection in SJL mice causes long-term central nervous system inflammation, potentially modeling human multiple sclerosis. This occurs without persistent viral RNA, highlighting a complex immune response in viral encephalitis.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Semliki Forest virus (SFV) infection in mice serves as a model for viral encephalitis and demyelinating diseases.
- The M9 mutant of SFV is avirulent, making it suitable for studying long-term central nervous system (CNS) effects.
Purpose of the Study:
- To investigate the long-term effects of avirulent M9 SFV infection on the CNS of BALB/c and SJL mice.
- To correlate the presence of infectious virus, viral RNA, cytokine mRNA, and spinal cord lesions up to 360 days post-infection (d.p.i.).
Main Methods:
- Mice were infected with M9 SFV, and tissues were analyzed for infectious virus, viral RNA (E2 and nsP1 regions), and cytokine mRNA (interferon-gamma, tumor necrosis factor-alpha).
- Reverse transcriptase polymerase chain reaction (RT-PCR) was used for molecular detection.
- Spinal cord lesions were assessed histologically.
Main Results:
- Infectious SFV was undetectable after 7 d.p.i. in both mouse strains.
- Viral RNA persisted up to 90 d.p.i. in both strains.
- Cytokine mRNA expression lasted longer in SJL mice (up to 360 d.p.i.) compared to BALB/c mice (up to 28 d.p.i.).
- Inflammatory lesions correlated with cytokine mRNA expression and were observed in SJL mice at 90 d.p.i., but not in BALB/c mice beyond 28 d.p.i.
Conclusions:
- M9 SFV infection induces prolonged pro-inflammatory cytokine expression in the CNS of SJL mice, independent of persistent viral genome.
- This prolonged cytokine response in SJL mice suggests a potential model for human multiple sclerosis pathogenesis.
- BALB/c mice exhibited a shorter-term inflammatory response to M9 SFV infection.