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J. Virol. doi:10.1128/JVI.00090-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

THE INDUCTION OF APOPTOSIS BY THE SEVERE ACUTE RESPIRATORY SYNDROME (SARS)-CORONAVIRUS 7a PROTEIN IS DEPENDENT ON ITS INTERACTION WITH THE Bcl-X_L PROTEIN

Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, Singapore; Victorian Infectious Diseases Reference Laboratory, North Melbourne, Victoria, Australia; Mechanisms of Apoptosis in Mammalian Cells Group, Institute of Molecular and Cell Biology, Singapore

^* To whom correspondence should be addressed. Email: mcbtanyj{at}imcb.a-star.edu.sg.

	Abstract

The severe acute respiratory syndrome coronavirus (SARS-CoV) 7a protein, which is not expressed by other known coronaviruses, can induce apoptosis in various cell-lines. In this study, we show that the over-expression of Bcl-X_L, a pro-survival member of the Bcl-2 family, blocks 7a-induced apoptosis, suggesting that the mechanism for apoptosis induction by 7a is at the level or up-stream of the Bcl-2 family. Co-immunoprecipitation experiments showed that 7a interacts with Bcl-X_L and other pro-survival proteins (Bcl-2, Bcl-w, Mcl-1 and A1) but not with the pro-apoptotic proteins (Bax, Bak, Bad and Bid). A good correlation between the abilities of 7a deletion mutants to induce apoptosis and to interact with Bcl-X_L was observed, suggesting that 7a triggers apoptosis by interfering directly with the pro-survival function of Bcl-X_L. Interestingly, amino acids 224 and 225 within the C-terminal transmembrane domain of Bcl-X_L are essential for the interaction with the 7a protein, although the BH3 domain of Bcl-X_L also contributes to this interaction. In addition, fractionation experiments showed that 7a co-localized with Bcl-X_L at the endoplasmic reticulum as well as the mitochondria, suggesting that they may form complexes in different membranous compartments.

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• Schaecher, S. R., Touchette, E., Schriewer, J., Buller, R. M., Pekosz, A. (2007). Severe Acute Respiratory Syndrome Coronavirus Gene 7 Products Contribute to Virus-Induced Apoptosis. J. Virol. 81: 11054-11068 [Abstract] [Full Text]