Induction of Apoptosis by the Severe Acute Respiratory Syndrome Coronavirus 7a Protein Is Dependent on Its Interaction with the Bcl-X sub(L) Protein

• Published in: Journal of virology 2007-06, Vol.81 (12), p.6346-6355
• Main Authors: Tan, Ying-Xim, Tan, Timothy HP, Lee, Marvin J-R, Tham, Puay-Yoke, Gunalan, Vithiagaran, Druce, Julian, Birch, Chris, Catton, Mike, Fu, Nai Yang, Yu, Victor C, Tan, Yee-Joo
• Format: Article
• Language: English
• Subjects: SARS coronavirus
• ISSN: 0022-538X; 1098-5514

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 overexpression of Bcl-X sub(L), a prosurvival member of the Bcl-2 family, blocks 7a-induced apoptosis, suggesting that the mechanism for apoptosis induction by 7a is at the level of or upstream from the Bcl-2 family. Coimmunoprecipitation experiments showed that 7a interacts with Bcl-X sub(L) and other prosurvival proteins (Bcl-2, Bcl-w, Mcl-1, and A1) but not with the proapoptotic 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 sub(L) was observed, suggesting that 7a triggers apoptosis by interfering directly with the prosurvival function of Bcl-X sub(L). Interestingly, amino acids 224 and 225 within the C-terminal transmembrane domain of Bcl-X sub(L) are essential for the interaction with the 7a protein, although the BH3 domain of Bcl-X sub(L) also contributes to this interaction. In addition, fractionation experiments showed that 7a colocalized with Bcl-X sub(L) at the endoplasmic reticulum as well as the mitochondria, suggesting that they may form complexes in different membranous compartments.