Viral Inhibitor of Apoptosis vFLIP/K13 Protects Endothelial Cells against Superoxide-Induced Cell Death
Viral Inhibitor of Apoptosis vFLIP/K13 Protects Endothelial Cells against Superoxide-Induced Cell Death
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DOI：
10.1128/jvi.00629-08
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发表时间：
2008-11
影响因子：
5.4
通讯作者：
M. Thurau;Gaby Marquardt;N. Gonin-Laurent;Kristina Weinländer;E. Naschberger;Ramona Jochmann;K. Alkharsah;T. Schulz;M. Thome;F. Neipel;M. Stürzl
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文献类型：
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作者：
M. Thurau;Gaby Marquardt;N. Gonin-Laurent;Kristina Weinländer;E. Naschberger;Ramona Jochmann;K. Alkharsah;T. Schulz;M. Thome;F. Neipel;M. Stürzl
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.
