Viral inhibitor of apoptosis vFLIP/K13 protects endothelial cells against superoxide-induced cell death

Thurau M, Marquardt G, Britzen-Laurent N, Weinlaender K, Naschberger E, Jochmann R, Alkharsah KR, Schulz TF, Thome M, Neipel F, Stürzl M (2009)

Publication Type: Journal article

Publication year: 2009

Journal

Book Volume: 83

Pages Range: 598-611

Journal Issue: 2

DOI: 10.1128/JVI.00629-08

Abstract

Human herpesvirus 8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS). HHV-8 encodes an antiapoptotic viral Fas-associated death domain-like interleukin-1β-converting enzyme-inhibitory protein (vFLIP/K13). The antiapoptotic activity of vFLIP/K13 has been attributed to an inhibition of caspase 8 activation and more recently to its capability to induce the expression of antiapoptotic proteins via activation of NF-κB. Our study provides the first proteome-wide analysis of the effect of vFLIP/K13 on cellular-protein expression. Using comparative proteome analysis, we identified manganese superoxide dismutase (MnSOD), a mitochondrial antioxidant and an important antiapoptotic enzyme, as the protein most strongly upregulated by vFLIP/K13 in endothelial cells. MnSOD expression was also upregulated in endothelial cells upon infection with HHV-8. Microarray analysis confirmed that MnSOD is also upregulated at the RNA level, though the differential expression at the RNA level was much lower (5.6-fold) than at the protein level (25.1-fold). The induction of MnSOD expression was dependent on vFLIP/K13-mediated activation of NF-κB, occurred in a cell-intrinsic manner, and was correlated with decreased intracellular superoxide accumulation and increased resistance of endothelial cells to superoxide-induced death. The upregulation of MnSOD expression by vFLIP/K13 may support the survival of HHV-8-infected cells in the inflammatory microenvironment in KS. Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Authors with CRIS profile

Involved external institutions

Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Université de Lausanne (UNIL) Switzerland (CH)

How to cite

APA:

Thurau, M., Marquardt, G., Britzen-Laurent, N., Weinlaender, K., Naschberger, E., Jochmann, R.,... Stürzl, M. (2009). Viral inhibitor of apoptosis vFLIP/K13 protects endothelial cells against superoxide-induced cell death. Journal of Virology, 83(2), 598-611. https://doi.org/10.1128/JVI.00629-08

MLA:

Thurau, Mathias, et al. "Viral inhibitor of apoptosis vFLIP/K13 protects endothelial cells against superoxide-induced cell death." Journal of Virology 83.2 (2009): 598-611.

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