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  2. Characteristics of enterovirus 71-induced cell death and genome scanning to identify viral genes involved in virus-induced cell apoptosis

Characteristics of enterovirus 71-induced cell death and genome scanning to identify viral genes involved in virus-induced cell apoptosis

  • Virus Res. 2019 May;265:104-114. doi: 10.1016/j.virusres.2019.03.017.
Jinjin Bai 1 Xixi Chen 1 Qingqing Liu 2 Xin Zhou 1 Jian-Er Long 3
Affiliations

Affiliations

  • 1 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032, China.
  • 2 Laboratory of Medical Microbiology, Department of Medical Microbiology and Parasitology, Shanghai Medical College of Fudan University, 138 Yixueyuan R., Shanghai 200032, China.
  • 3 Key Laboratory of Medical Molecular Virology of Ministries of Education and Health, Shanghai Medical College of Fudan University, Shanghai 200032, China; Laboratory of Medical Microbiology, Department of Medical Microbiology and Parasitology, Shanghai Medical College of Fudan University, 138 Yixueyuan R., Shanghai 200032, China. Electronic address: longjianer@fudan.edu.cn.
Abstract

Enterovirus 71 (EV71) causes hand-foot-and-mouth disease and severe neural complications in infants and young children. Viral pathogenesis is associated with virus-induced cell death and inflammatory cytokine production, which is usually correlated with the type of programmed cell death. EV71-infected cells were analyzed through microscopy, cell staining, and immunoblotting to determine the characteristics of EV71-induced cell death. Results demonstrated that EV71 Infection induced cell shrinkage, nuclear condensation, decreased mitochondrial potential, and membrane phosphatidylserine translocation. Caspase-9 activation, poly (ADP-ribose) polymerase cleavage, and Lactate Dehydrogenase release were also observed during virus-induced cell death. The activated gasdermin D (GSDMD) and the phosphorylated Mixed Lineage Kinase domain-like protein (p-MLKL) were not detected. These observations indicated that EV71-induced cell death was mainly executed by Apoptosis through the intrinsic pathway rather than by GSDMD-mediated Pyroptosis and p-MLKL-mediated Necroptosis. Genome scanning analysis identified that EV71 2A, 2B, and 3C might be the determinant genes of virus-induced cell death. Further experiments showed that EV71 2A- and 3C-induced cell death exhibited dependence on their Protease activities but involved different mechanisms. EV71 2A-induced cell death was correlated with the shut-off of host cap-dependent translation, whereas EV71 3C-induced cell death might not be ascribed to this mechanism. These findings would enhance our understanding of EV71 Infection and viral pathogenesis, and help identify Antiviral targets.

Keywords

Apoptosis; Genome scanning; Nterovirus 71; Programmed cell death.

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