title: The NS1 protein of influenza A virus interacts with heat shock protein Hsp90 in human alveolar basal epithelial cells: implication for virus-induced apoptosis.
abstract: BACKGROUND
  Our previous study showed that the NS1 protein of highly pathogenic avian influenza A virus H5N1 induced caspase-dependent apoptosis in human alveolar basal epithelial cells (A549), supporting its function as a proapoptotic factor during viral infection, but the mechanism is still unknown.
  
  
  RESULTS
  To characterize the mechanism of NS1-induced apoptosis, we used a two-hybrid system to isolate the potential NS1-interacting partners in A549 cells. We found that heat shock protein 90 (Hsp90) was able to interact with the NS1 proteins derived from both H5N1 and H3N2 viruses, which was verified by co-immunoprecitation assays. Significantly, the NS1 expression in the A549 cells dramatically weakened the interaction between Apaf-1 and Hsp90 but enhanced its interaction with cytochrome c (Cyt c), suggesting that the competitive binding of NS1 to Hsp90 might promote the Apaf-1 to associate with Cyt c and thus facilitate the activation of caspase 9 and caspase 3.
  
  
  CONCLUSIONS
  The present results demonstrate that NS1 protein of Influenza A Virus interacts with heat hock protein Hsp90 and meidates the apoptosis induced by influenza A virus through the caspase cascade.
authors.affiliation: Institute of Biotechnology, Academy of Military Medical Sciences, Beijing 100071, P.R. China.
authors.forename: Chuanfu
authors.initials: C
authors.lastname: Zhang
authors.forename: Yutao
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Zhou
authors.forename: Zhixin
authors.initials: Z
authors.lastname: Yang
authors.forename: Xuelin
authors.initials: X
authors.lastname: Liu
authors.forename: Zhiliang
authors.initials: Z
authors.lastname: Cao
authors.forename: Hongbin
authors.initials: H
authors.lastname: Song
authors.forename: Yuxian
authors.initials: Y
authors.lastname: He
authors.forename: Peitang
authors.initials: P
authors.lastname: Huang
mesh_terms: D017209:Apoptosis; D002460:Cell Line; D004847:Epithelial Cells / Q000821:virology*; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D047468:Immunoprecipitation; D053122:Influenza A Virus, H3N2 Subtype / Q000472:pathogenicity*; D053124:Influenza A Virus, H5N1 Subtype / Q000472:pathogenicity*; D007251:Influenza, Human / Q000473:pathology*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
chemical_list: D018841:HSP90 Heat-Shock Proteins; C085820:INS1 protein, influenza virus; D017361:Viral Nonstructural Proteins