| First Author | Yang Y | Year | 2005 |
| Journal | Biochem J | Volume | 392 |
| Issue | Pt 1 | Pages | 135-43 |
| PubMed ID | 16048439 | Mgi Jnum | J:287050 |
| Mgi Id | MGI:6414714 | Doi | 10.1042/BJ20050698 |
| Citation | Yang Y, et al. (2005) Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors. Biochem J 392(Pt 1):135-43 |
| abstractText | One of the hallmark findings in patients suffering from SARS (severe acute respiratory syndrome) is lymphopenia, which is the result of massive lymphocyte death. SARS-CoV (SARS coronavirus), a novel coronavirus that has been etiologically associated with SARS cases, is homologous with MHV (murine hepatitis coronavirus), and MHV small envelope E protein is capable of inducing apoptosis. We hypothesized that SARS-CoV encodes a small envelope E protein that is homologous with MHV E protein, thus inducing T-cell apoptosis. To test this hypothesis, a cDNA encoding SARS-CoV E protein was created using whole gene synthesis. Our results showed that SARS-CoV E protein induced apoptosis in the transfected Jurkat T-cells, which was amplified to higher apoptosis rates in the absence of growth factors. However, apoptosis was inhibited by overexpressed antiapoptotic protein Bcl-xL. Moreover, we found that SARS-CoV E protein interacted with Bcl-xL in vitro and endogenous Bcl-xL in vivo and that Bcl-xL interaction with SARS-CoV E protein was mediated by BH3 (Bcl-2 homology domain 3) of Bcl-xL. Finally, we identified a novel BH3-like region located in the C-terminal cytosolic domain of SARS-CoV E protein, which mediates its binding to Bcl-xL. These results demonstrate, for the first time, a novel molecular mechanism of T-cell apoptosis that contributes to the SARS-CoV-induced lymphopenia observed in most SARS patients. |
