1. Academic Validation
  2. Proteomic and phosphoproteomic analysis of responses to enterovirus A71 infection reveals novel targets for antiviral and viral replication

Proteomic and phosphoproteomic analysis of responses to enterovirus A71 infection reveals novel targets for antiviral and viral replication

  • Antiviral Res. 2023 Nov 20:105761. doi: 10.1016/j.antiviral.2023.105761.
Dandan Lin 1 Xiaojing Dong 1 Xia Xiao 1 Zichun Xiang 1 Xiaobo Lei 2 Jianwei Wang 3
Affiliations

Affiliations

  • 1 NHC Key Laboratory of System Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, PR China.
  • 2 NHC Key Laboratory of System Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, PR China. Electronic address: fyleixb@126.com.
  • 3 NHC Key Laboratory of System Biology of Pathogens and Christophe Mérieux Laboratory, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100730, PR China. Electronic address: wangjw28@163.com.
Abstract

Hand, foot, and mouth disease (HFMD) is a common infectious disease in infants and children, especially those under five years of age. EV-A71 is a common pathogen that causes HFMD and the primary pathogen leading to severe or fatal HFMD, which is characterized by neurological complications. However, the underlying mechanisms of EV-A71 pathogenesis remain largely unknown. In this report, we used proteomic and phosphorylated proteomic methods to characterize the proteome and phosphoproteome profiles of EV-A71-infected human neuroblastoma SK-N-SH cells. More than 7744 host proteins and 10069 phosphorylation modification sites were successfully quantified. Among them, 974 proteins and 3648 phosphorylation modification sites were regulated significantly during EV-A71 Infection. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis revealed that EV-A71 altered cell biological processes, including protein synthesis, RNA splicing and metabolism in SK-N-SH cells. Notably, based on the prediction of upregulated kinases during EV-A71 Infection, we identified specific kinase inhibitors approved by the FDA, with ceralasertib, bosutinib, flavin mononucleotide, minocycline, pimasertib and acetylcysteine inhibiting EV-A71 Infection. Finally, EV-A71 proteins were found to be phosphorylated during Infection, with one site (S184 on 3D polymerase) observed to be crucial for viral replication because a S184A mutation knocked out viral replication. The results improve our understanding of the host response to EV-A71 Infection of neuroblastoma cells and provide potential targets for developing anti-EV-A71 strategies.

Keywords

EV-A71; Phosphoproteome; Proteome; RNA-Dependent RNA polymerase; SK-N-SH.

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