Bcl-xL inhibits T-cell apoptosis induced by expression of SARS coronavirus E protein in the absence of growth factors
Authors: Hong Wang
Sheng Zhang
Xiao-Feng Yang
Bernard Ng
Fan Yang
John Brendese
Huifang Lu
Zeyu Xiong
Yu Yang
Justin Nguyen
Yan Yan
Journal: Biochemical Journal (2005)
Discipline: BIOLOGY & BIOCHEMISTRY
Keywords: SARS; lymphopenia; coronavirus; apoptosis; T-cell
Affiliations: Department of Medicine, Laboratory of Immunopathology, Biology of Inflammation Center, Baylor College of Medicine, Houston, TX 77030, U.S.A., Section of Atherosclerosis and Lipoprotein Research, Baylor College of Medicine, Houston, TX 77030, U.S.A., Department of Immunology, Baylor College of Medicine, Houston, TX 77030, U.S.A.

Abstract:  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. 

Retracted: No

PubPeer comments:
 Brought to my attention by a reader. Figure 2B. * Red boxes: Two panels in the  Serum withdrawal row appear to show a similar graph, but different gated percentages. ![file] , 
 Figure 3E. * Green arrows: Lanes 1 and 7 appear to look similar * Blue arrows: Lanes 6 and 8 appear to look similar ![file] , 
 Figure 3F. * Pink arrows: Lanes 1, 2, and 9 appear to look similar to each other. ![file] , 
 Figure 3E of this paper looks unexpectedly similar to Figure 2F in another 2015 paper by the same research group, i.e. Yu Yang et al. - An N-terminal region of translationally controlled tumor protein is required for its antiapoptotic activity - Oncogene (2005) 24, 4778u20134788 - DOI: 10.1038 sj.onc.1208666 - See: https: pubpeer.com publications F9C2906010A2C0DF6DE4D9A50D3628. In the Oncogene (2005) paper, the panel shows a 26 kD protein called Bcl-xL-TNT, while in this Biochem J (2005) paper, it represents a 12.5 kD protein. The peptide concentrations also do not appear to match. It looks like the Oncogene panel might be the original one, since it does not show repetitive features. ![file] , 
 Figure 3B from this paper looks very similar to Figure 1B from the Oncogene (2005) paper, where it represents a slightly different set of samples. Shown here with purple boxes. ![file] , 
 #3 If I may intervene for a moment, I think you have marked up the low resolution figure in the articleu2019s pdf? The higher resolution figures available at PubMedCentral are pretty much pixel perfect with regards to the shared objects in the replicated lanes of these purported autoradiograms. https: www.ncbi.nlm.nih.gov pmc articles PMC1317672 figure F3 It is currently fashionable to decry an avalanche of appalling science being unleashed by Covid-19. As you probably know better than most, there will have been no change in the ratio of good-versus-bonkers research published due to the pandemic. This particular disaster was published fifteen years ago. u2019Twas ever thus. , 
 #6. Not sure if an intervention was needed. The similarities were clear from the version I used. , 
 #6 I think this is a very practical suggestion. PMC often provides clear images, but the disadvantage is that it is not convenient to save files, so I usually take screenshots. ![file] ,