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Antiviral effects of pan-caspase inhibitors on the replication of coxsackievirus B3

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Abstract

The induction of apoptosis during coxsackievirus B3 (CVB3) infection is well documented. In order to study whether the inhibition of apoptosis has an impact on CVB3 replication, the pan-caspase inhibitor Z-VAD-FMK was used. The decreased CVB3 replication is based on reduced accumulation of both viral RNA and viral proteins. These effects are due to an inhibitory influence of Z-VAD-FMK on the proteolytic activity of the CVB3 proteases 2A and 3C, which was demonstrated by using the target protein poly(A)-binding protein (PABP). The antiviral effect of the structurally different pan-caspase inhibitor Q-VD-OPH was independently of the viral protease inhibition and resulted in suppression of virus progeny production and impaired release of newly produced CVB3 from infected cells. A delayed release of cytochrome c into the cytoplasm was detected in Q-VD-OPH-treated CVB3-infected cells pointing to an involvement of caspases in the initial steps of mitochondrial membrane-permeabilization.

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Acknowledgments

This work was supported by Deutsche Forschungsgemeinschaft grant HE 2910/6-1. Purified 2A protease of CVB3 was kindly provided by Dr. Joachim Seipelt at the Max. F. Perutz Laboratories, University Departments at the Vienna Biocenter, Department of Medical Biochemistry, Medical University Vienna. The plasmid pET28a (N-terminal His6-tag on PABP) was kindly provided by Dr. Matthias Görlach, Leibniz Institute for Age Research − Fritz-Lipmann-Institute e.V., Jena, Germany.

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Authors and Affiliations

  1. Institute of Virology and Antiviral Therapy, Medical Center, Friedrich Schiller University, Hans-Knöll-Str. 2, D-07745, Jena, Germany

    Ulrike Martin, Nadine Jarasch, Simone Seitz, Roland Zell, Peter Wutzler & Andreas Henke

  2. Leibniz Institute for Age Research, Fritz-Lipmann-Institute e.V., Department of Molecular Biophysics/NMR, Beutenbergstr. 11a, D-07745, Jena, Germany

    Matthias Nestler

  3. Leibniz Institute for Natural Product Research and Infection Biology, Hans-Knöll-Institute, Department of Cell and Molecular Biology, Beutenbergstr. 11a, D-07745, Jena, Germany

    Alexander Rassmann & Thomas Munder

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  1. Ulrike Martin
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Correspondence to Andreas Henke.

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Martin, U., Jarasch, N., Nestler, M. et al. Antiviral effects of pan-caspase inhibitors on the replication of coxsackievirus B3. Apoptosis 12, 525–533 (2007). https://doi.org/10.1007/s10495-006-0015-y

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