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 eff ect with subsequent death of host cells. We now show that SV infection trig gers an apoptotic program in target cells. Incubation of infected cells wit h the peptide inhibitor z-VAD-fmk abrogated SV-induced apoptosis, indicatin g 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 trigger ed by death receptors, including CD95 and tumor necrosis factor (TNF)-R1. I n 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 infl uence the maturation and budding of SV progeny. In conclusion, SV-induced c ell injury is mediated by CD95- and TNF-R1-independent activation of caspas es, leading to the death of host cells without impairment of the viral life cycle.