The interplays between autophagy and apoptosis induced by enterovirus 71

PLoS One. 2013;8(2):e56966. doi: 10.1371/journal.pone.0056966. Epub 2013 Feb 20.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Retracted Publication

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Apoptosis*
  • Autophagy*
  • Caspases / metabolism
  • Cathepsins / metabolism
  • Cell Line
  • Enterovirus A, Human / physiology*
  • Humans
  • Lysosomes
  • Microtubule-Associated Proteins / metabolism
  • Phagosomes / metabolism
  • Proteolysis
  • Sequestosome-1 Protein
  • Virus Release


  • Adaptor Proteins, Signal Transducing
  • MAP1LC3A protein, human
  • Microtubule-Associated Proteins
  • SQSTM1 protein, human
  • Sequestosome-1 Protein
  • Cathepsins
  • Caspases

Grants and funding

This work was supported by grants from National Natural Science Foundation of China (NSFC 31270200), National Basic Research Program of China (973 Project, 2011CB504903), Eleven-fifth Mega-Scientific project on “prevention and treatment of AIDS, viral hepatitis and other infectious diseases” (2009ZX10004-303). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.