期刊
BIOCHEMICAL JOURNAL
卷 392, 期 -, 页码 135-143出版社
PORTLAND PRESS LTD
DOI: 10.1042/BJ20050698
关键词
Bcl-xL; lymphopenia; protein-protein interaction; severe acute respiratory syndrome (SARS) virus; SARS-CoV E protein; T-cell apoptosis
资金
- NCI NIH HHS [P20 CA103698] Funding Source: Medline
- NIAID NIH HHS [K08 AI054514, AI054514] Funding Source: Medline
- NIDDK NIH HHS [R01 DK056238, P30 DK56238] Funding Source: Medline
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 BclxL 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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据