Activation of the Mitochondrial Apoptotic Signaling Platform during Rubella Virus Infection
by
Claudia Claus 1,*,†, Lena Manssen 1,†, Denise Hübner 1, Sarah Roßmark 1, Viktoria Bothe 2, Alice Petzold 1, Claudia Große 1, Mareen Reins 1, Annette Mankertz 3, Teryl K. Frey 4 and Uwe G. Liebert 1
Claudia Claus 1,*,†, Lena Manssen 1,†, Denise Hübner 1, Sarah Roßmark 1, Viktoria Bothe 2, Alice Petzold 1, Claudia Große 1, Mareen Reins 1, Annette Mankertz 3, Teryl K. Frey 4 and Uwe G. Liebert 1
1
Institute of Virology, University of Leipzig, 04103 Leipzig, Germany
2
Division of Clinical Pharmacology, Ludwig-Maximilian University Munich, 80336 Munich, Germany
3
WHO European Regional Reference Laboratory for Measles and Rubella, Robert Koch-Institute, 13353 Berlin, Germany
4
Department of Biology, Georgia State University, Atlanta, GA 30303, USA
*
Author to whom correspondence should be addressed.
†
These authors contributed equally to this work.
Academic Editor: Curt Hagedorn
Viruses 2015, 7(12), 6108-6126; https://doi.org/10.3390/v7122928
Received: 3 August 2015 / Revised: 16 November 2015 / Accepted: 17 November 2015 / Published: 26 November 2015
(This article belongs to the Section Antivirals & Vaccines)
Mitochondria- as well as p53-based signaling pathways are central for the execution of the intrinsic apoptotic cascade. Their contribution to rubella virus (RV)-induced apoptosis was addressed through time-specific evaluation of characteristic parameters such as permeabilization of the mitochondrial membrane and subsequent release of the pro-apoptotic proteins apoptosis-inducing factor (AIF) and cytochrome c from mitochondria. Additionally, expression and localization pattern of p53 and selected members of the multifunctional and stress-inducible cyclophilin family were examined. The application of pifithrin μ as an inhibitor of p53 shuttling to mitochondria reduced RV-induced cell death to an extent similar to that of the broad spectrum caspase inhibitor z-VAD-fmk (benzyloxycarbonyl-V-A-D-(OMe)-fmk). However, RV progeny generation was not altered. This indicates that, despite an increased survival rate of its cellular host, induction of apoptosis neither supports nor restricts RV replication. Moreover, some of the examined apoptotic markers were affected in a strain-specific manner and differed between the cell culture-adapted strains: Therien and the HPV77 vaccine on the one hand, and a clinical isolate on the other. In summary, the results presented indicate that the transcription-independent mitochondrial p53 program contributes to RV-induced apoptosis.
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Keywords:
mPTP; p53; AIF; cyclophilin family; CypA; Cyp40; cytochrome c; NIM811; PFTμ
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited
MDPI and ACS Style
Claus, C.; Manssen, L.; Hübner, D.; Roßmark, S.; Bothe, V.; Petzold, A.; Große, C.; Reins, M.; Mankertz, A.; Frey, T.K.; Liebert, U.G. Activation of the Mitochondrial Apoptotic Signaling Platform during Rubella Virus Infection. Viruses 2015, 7, 6108-6126.
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