The interplays between autophagy and apoptosis induced by enterovirus 71
Authors: Xiaoyan Zhang
Zhendong Zhao
He Huang
Xueyan Xi
Tao Wang
Jianwei Wang
Qi Jin
Ji Wang
Bei Wang
Journal: PLoS ONE (2013)
Discipline: Multidisciplinary
Keywords: Enterovirus 71; EV71; autophagy; apoptosis; viral pathogenesis
Affiliations: MOH Key Laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.

Abstract:  Background: Enterovirus 71 (EV71) is the causative agent of human diseases with distinct severity, from mild hand, foot and mouth disease to severe neurological syndromes, such as encephalitis and meningitis. The lack of understanding of viral pathogenesis as well as lack of efficient vaccine and drugs against this virus impedes the control of EV71 infection. EV71 virus induces autophagy and apoptosis; however, the relationship between EV71-induced autophagy and apoptosis as well as the influence of autophagy and apoptosis on virus virulence remains unclear. Methodology/principal findings: In this study, it was observed that the Anhui strain of EV71 induced autophagy and apoptosis in human rhabdomyosarcoma (RD-A) cells. Additionally, by either applying chemical inhibitors or knocking down single essential autophagic or apoptotic genes, inhibition of EV71 induced autophagy inhibited the apoptosis both at the autophagosome formation stage and autophagy execution stage. However, inhibition of autophagy at the stage of autophagosome and lysosome fusion promoted apoptosis. In reverse, the inhibition of EV71-induced apoptosis contributed to the conversion of microtubule-associated protein 1 light chain 3-I (LC3-I) to LC3-II and degradation of sequestosome 1 (SQSTM1/P62). Furthermore, the inhibition of autophagy in the autophagsome formation stage or apoptosis decreased the release of EV71 viral particles. Conclusions/significance: In conclusion, the results of this study not only revealed novel aspect of the interplay between autophagy and apoptosis in EV71 infection, but also provided a new insight to control EV71 infection. 

Retracted: Yes

PubPeer comments:
 Concern about Figure 2B: Several areas in the four FACS panels appear to be visible multiple times, sometimes between the panels or within the same panel. Ellipses of the same color show several of these areas.  Reported to the journal in September 2014. , 
 Concern about Figure 5A. Two bands in the PARP panel look very similar to each other. Shown with red boxes.  , 
 #1 This problem was raised and solved five years ago. In early 2015, we were required to provide raw data for figure 2B and 5A by the Editorial Office of PLoS One. We re-conducted the experiments back-to-back by two authors in the authorship and provided the raw data as well as the description of how these data generated to the journal office. The following screenshots are the email with the journal staff of PLoS One at that time. We provided the corrected data in 2015, but the journal did not replace the original figures in the paper. The attached files are corrected data provided to the editorial office in 2015.       , 
 Dear Dr. Zhao, Thank you for your reply. I don t think the issue has been resolved at all, at least it has not been for me and for the scientific community. What happened to these figures that could explain these repetitive patterns and bands? Just replacing these figures with other ones is not going to resolve the grave concerns I have about this paper. , 
 2021 retraction. https: journals.plos.org plosone article?id=10.1371 journal.pone.0246985 Following the publication of this article [1], concerns were raised regarding results reported in Figs 1, 2, 3, 5, 6, and 7. Specifically, In Fig 1C, the background directly surrounding the bands presented in the LC3I LC3II blot does not appear to match the overall background of the blot. In Fig 2B, multiple repetitive clusters of signal have been detected within and between the reported FACS data. The similarity of the signal between these panels is greater than would be expected from independent FACS samples. The following bands appear similar: - Fig 3A, P62 panel: lane 3 and lane 7. - Fig 3C, PARP panel: lane 1 and lane 4 when flipped. - Fig 3C, Beclin1 panel: lane 1 and lane 3. - Fig 5A, PARP panel: lane 4 and lane 6. - Fig 5A, Caspase-p panel: lane 1 and lane 3. - Fig 5A, LC3-I panel: lanes 1, 2 and lanes 3, 4 respectively. - Fig 5A, LC3-II panel: lanes 1, 2 and lanes 3, 4 respectively. - Fig 5A, P62 panel: lanes 5, 6 and lanes 7, 8 respectively. The PARP panel of Fig 3A appears similar to the PARP panel of Fig 6A despite being used to represent different experimental conditions. The Actin panel of Fig 5A appears similar to the Actin panel of Fig 7A despite being used to represent different experimental conditions. The original data underlying the published figures are no longer available. The authors provided repeat experiment data to support some of the experiments for which questions were raised, but the data did not resolve the concerns. In light of the concerns affecting multiple figure panels that question the integrity of these data and the unavailability of the data underlying the published results, the PLOS ONE Editors retract this article. XX, XZ, BW, TW, JiW, HH, JiaW, QJ, and ZZ either did not respond to the retraction or could not be reached. Reference 1. Xi X, Zhang X, Wang B, Wang T, Wang J, Huang H, et al. (2013) The Interplays between Autophagy and Apoptosis Induced by Enterovirus 71. PLoS ONE 8(2): e56966. https: doi.org 10.1371 journal.pone.0056966 pmid:23437282 ,