title: The Novel H7N9 Influenza A Virus NS1 Induces p53-Mediated Apoptosis of A549 Cells.
abstract: BACKGROUND
  H7N9, emerged as an avian influenza virus outbreak in Eastern China in early 2013, and represented another major threat to global health. Roles of its NS1 protein, an essential viral factor, in regulating apoptosis remain unknown.
  
  
  METHODS
  Apoptotic effect and features of H7N9/NS1 in the human A549 alveolar basal epithelial cell line were examined by caspase 3/7 activity assay and western blotting of apoptotic associated proteins. Effects of H7N9/NS1on mitochondrial membrane potential were investigated by flow cytometry.
  
  
  RESULTS
  The expression of H7N9/NS1 in A549 cells activated caspase 3/7 and increased the protein levels of cleaved caspase 7 and cleaved poly (ADP-ribose) polymerase (PARP). H7N9/NS1-expressing A549 cells displayed a decrease in mitochondrial membrane potential. In addition, H7N9/NS1 increased the protein levels of total p53, p53 phosphorylated at Ser46 and Ser37, activated caspase 9, and the Bax/Bcl-2 ratio.
  
  
  CONCLUSIONS
  Our results suggest that H7N9/NS1 protein causes the accumulation of p53 by increasing phosphorylation levels of p53 and the induction of mitochondrial dysfunction, which may contribute to H7N9/NS1-induced apoptosis in A549 cells.
authors.forename: Yinxia
authors.initials: Y
authors.lastname: Yan
authors.forename: Yongming
authors.initials: Y
authors.lastname: Du
authors.forename: Gefei
authors.initials: G
authors.lastname: Wang
authors.forename: Yuxue
authors.initials: Y
authors.lastname: Deng
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.forename: Kangsheng
authors.initials: K
authors.lastname: Li
mesh_terms: D000072283:A549 Cells; D000595:Amino Acid Sequence; D017209:Apoptosis; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D006801:Humans; D064766:Influenza A Virus, H7N9 Subtype / Q000378:metabolism*; D053078:Membrane Potential, Mitochondrial; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D016415:Sequence Alignment; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D015854:Up-Regulation; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C085820:INS1 protein, influenza virus; D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53; D017361:Viral Nonstructural Proteins; D051028:bcl-2-Associated X Protein; D011065:Poly(ADP-ribose) Polymerases; D053148:Caspase 3; D053179:Caspase 7