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Sendai virus infection induces apoptosis through activation of caspase-8 (FLICE) and caspase-3 (CPP32)
1Abteilung Innere Medizin I, Medizinische Universitätsklinik Tübingen, 72076 Tübingen, Germany. michael.bitzer@uni-tuebingen.de
Abstract:
Sendai virus (SV) infection and replication lead to a strong cytopathic effect with subsequent death of host cells. We now show that SV infection triggers an apoptotic program in target cells. Incubation of infected cells with the peptide inhibitor z-VAD-fmk abrogated SV-induced apoptosis, indicating that proteases of the caspase family were involved. Moreover, proteolytic activation of two distinct caspases, CPP32/caspase-3 and, as shown for the first time in virus-infected cells, FLICE/caspase-8, could be detected. So far, activation of FLICE/caspase-8 has been described in apoptosis triggered by death receptors, including CD95 and tumor necrosis factor (TNF)-R1. In contrast, we could show that SV-induced apoptosis did not require TNF or CD95 ligand. We further found that apoptosis of infected cells did not influence the maturation and budding of SV progeny. In conclusion, SV-induced cell injury is mediated by CD95- and TNF-R1-independent activation of caspases, leading to the death of host cells without impairment of the viral life cycle.
Insights
Sendai virus (SV) infection triggers apoptosis in host cells via caspase activation. This programmed cell death occurs independently of death receptors, allowing viral replication to continue unimpeded.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Sendai virus (SV) infection causes significant cell damage and death.
- Apoptosis, or programmed cell death, is a critical cellular process.
- Understanding viral-induced apoptosis mechanisms is crucial for antiviral strategies.
Purpose of the Study:
- To investigate the role of apoptosis in Sendai virus infection.
- To identify the specific molecular pathways involved in SV-induced cell death.
- To determine if SV-induced apoptosis affects viral replication.
Main Methods:
- Infection of host cells with Sendai virus.
- Treatment with caspase inhibitor z-VAD-fmk to assess protease involvement.
- Detection of caspase activation using specific assays.
- Analysis of viral progeny maturation and budding.
Main Results:
- SV infection triggers a robust apoptotic program in host cells.
- Caspase activation, including CPP32/caspase-3 and FLICE/caspase-8, is essential for SV-induced apoptosis.
- Apoptosis is independent of CD95 and TNF-R1 death receptor pathways.
- Host cell apoptosis does not impede Sendai virus maturation or budding.
Conclusions:
- Sendai virus induces host cell death through a CD95- and TNF-R1-independent caspase activation pathway.
- The viral life cycle remains unaffected by the induction of apoptosis.
- This study elucidates a novel mechanism of viral-induced cell death.