Sendai virus infection induces apoptosis through activation of caspase-8 (FLICE) and caspase-3 (CPP32).
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.
Bitzer
M
M
Abteilung Innere Medizin I, Medizinische Universitätsklinik Tübingen, 72076 Tübingen, Germany. michael.bitzer@uni-tuebingen.de
Prinz
F
F
Bauer
M
M
Spiegel
M
M
Neubert
W J
WJ
Gregor
M
M
Schulze-Osthoff
K
K
Lauer
U
U
D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000502:physiology*; D002460:Cell Line; D002642:Chick Embryo; D004789:Enzyme Activation; D000882:Haplorhini; D006801:Humans; D011480:Protease Inhibitors / Q000494:pharmacology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D018108:Respirovirus / Q000502:physiology*; D014779:Virus Replication; D019014:fas Receptor / Q000502:physiology
D011480:Protease Inhibitors; D018124:Receptors, Tumor Necrosis Factor; D019014:fas Receptor; C505407:CASP3 protein, human; C505530:CASP8 protein, human; C506433:CASP9 protein, human; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases