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Journal of Virology, January 1999, p. 702-708, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Sendai Virus Infection Induces Apoptosis through Activation of Caspase-8 (FLICE) and Caspase-3 (CPP32)

Michael Bitzer,1,* Florian Prinz,1 Manuel Bauer,1 Martin Spiegel,1 Wolfgang J. Neubert,2 Michael Gregor,1 Klaus Schulze-Osthoff,1 and Ulrich Lauer1

Abteilung Innere Medizin I, Medizinische Universitätsklinik Tübingen, 72076 Tübingen,1 and Abteilung für Virusforschung, Max-Planck-Institut für Biochemie, 82152 Martinsried,2 Germany

Received 12 January 1998/Accepted 5 October 1998

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.

* Corresponding author. Mailing address: Abteilung Innere Medizin I, Medizinische Universitätsklinik Tübingen, Otfried-Müller-Str. 10, 72076 Tübingen, Germany. Phone: (49) 7071-2983189. Fax: (49) 7071-292095. E-mail: michael.bitzer{at}uni-tuebingen.de.

Journal of Virology, January 1999, p. 702-708, Vol. 73, No. 1
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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