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Death mechanisms in cultured cells infected by Semliki Forest virus
G M Glasgow1, M M McGee, B J Sheahan
1Department of Microbiology, Moyne Institute of Preventive Medicine, Trinity College, Dublin, Ireland.
Abstract:
We have investigated the induction of cell death in cultured cells by the virulent SFV4 and avirulent A7 strains of Semliki Forest virus (SFV). In BHK cells, death occurred by a typical apoptotic mechanism, as did the death of oligodendrocytes in glial cell cultures. For cerebellar neuron cultures, virus-induced death was due to necrosis. Although the SFV4 and A7 strains did not differ in the mechanism of induction of cell death, the virulent SFV4 strain did multiply to a higher titre in cultured neurons than the avirulent A7 strain. This is consistent with previous animal studies which indicate that the virulence of SFV strains is controlled by rapidity of multiplication in the CNS, leading to a lethal threshold of damage, rather than differential cell tropism or cell death mechanisms. The immune-mediated demyelination induced by avirulent strains may be triggered by apoptosis of oligodendrocytes, the consequences of which are obscured by death for virulent strains.
Insights
Virulent and avirulent Semliki Forest virus (SFV) strains induce cell death via apoptosis or necrosis depending on cell type. Virulent SFV replicates faster in neurons, correlating with disease severity.
Area of Science:
- Neurovirology
- Cellular Biology
- Immunology
Background:
- Semliki Forest virus (SFV) is a neurotropic virus with varying virulence.
- Understanding SFV-induced cell death mechanisms is crucial for neurodegenerative disease research.
- Different cell types may exhibit distinct responses to viral infection.
Purpose of the Study:
- To investigate the mechanisms of cell death induced by virulent (SFV4) and avirulent (A7) Semliki Forest virus strains in cultured cells.
- To compare the replication kinetics of SFV strains in different neuronal and glial cell types.
- To correlate viral replication and cell death mechanisms with SFV virulence in the central nervous system (CNS).
Main Methods:
- Primary cell cultures (BHK cells, glial cells, cerebellar neurons) were infected with SFV4 and A7.
- Cell death mechanisms (apoptosis, necrosis) were assessed.
- Viral replication titers were quantified in different cell types.
Main Results:
- Both SFV strains induced apoptosis in BHK cells and oligodendrocytes.
- Cerebellar neurons underwent necrosis upon SFV infection.
- The virulent SFV4 strain replicated to higher titers in cultured neurons compared to the avirulent A7 strain.
- No significant difference in cell death mechanisms was observed between SFV strains within the same cell type.
Conclusions:
- SFV virulence is linked to rapid replication in CNS neurons, leading to a threshold of damage, rather than differential cell tropism or death mechanisms.
- Apoptosis of oligodendrocytes by avirulent SFV strains may contribute to immune-mediated demyelination.
- The rapid replication of virulent SFV strains may obscure the consequences of oligodendrocyte apoptosis.