Bitzer M, Prinz F, Bauer M, Spiegel M, Neubert W J, Gregor M, Schulze-Osthoff K, Lauer U
Abteilung Innere Medizin I, Medizinische Universitätsklinik Tübingen, 72076 Tübingen, Germany.
J Virol. 1999 Jan;73(1):702-8. doi: 10.1128/JVI.73.1.702-708.1999.
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.
仙台病毒（SV）的感染与复制会引发强烈的细胞病变效应，随后导致宿主细胞死亡。我们现在证明，SV感染会在靶细胞中触发凋亡程序。用肽抑制剂z-VAD-fmk孵育感染细胞可消除SV诱导的凋亡，这表明半胱天冬酶家族的蛋白酶参与其中。此外，还能检测到两种不同的半胱天冬酶，即CPP32/半胱天冬酶-3以及首次在病毒感染细胞中发现的FLICE/半胱天冬酶-8的蛋白水解激活。到目前为止，FLICE/半胱天冬酶-8的激活已在由死亡受体（包括CD95和肿瘤坏死因子（TNF）-R1）触发的凋亡中被描述。相比之下，我们可以证明SV诱导的凋亡不需要TNF或CD95配体。我们进一步发现，感染细胞的凋亡并不影响SV子代的成熟和出芽。总之，SV诱导的细胞损伤是由半胱天冬酶的CD95和TNF-R1非依赖性激活介导的，导致宿主细胞死亡而不损害病毒生命周期。
