title: The distinct binding properties between avian/human influenza A virus NS1 and Postsynaptic density protein-95 (PSD-95), and inhibition of nitric oxide production.
abstract: BACKGROUND
  The NS1 protein of influenza A virus is able to bind with many proteins that affect cellular signal transduction and protein synthesis in infected cells. The NS1 protein consists of approximately 230 amino acids and the last 4 amino acids of the NS1 C-terminal form a PDZ binding motif. Postsynaptic Density Protein-95 (PSD-95), which is mainly expressed in neurons, has 3 PDZ domains. We hypothesise that NS1 binds to PSD-95, and this binding is able to affect neuronal function.
  
  
  RESULTS
  We conducted a yeast two-hybrid analysis, GST-pull down assays and co-immunoprecipitations to detect the interaction between NS1 and PSD-95. The results showed that NS1 of avian influenza virus H5N1 (A/chicken/Guangdong/1/2005) is able to bind to PSD-95, whereas NS1 of human influenza virus H1N1 (A/Shantou/169/2006) is unable to do so. The results also revealed that NS1 of H5N1 significantly reduces the production of nitric oxide (NO) in rat hippocampal neurons.
  
  
  CONCLUSIONS
  In summary, our study indicates that NS1 of influenza A virus can bind with neuronal PSD-95, and the avian H5N1 and human H1N1 influenza A viruses possess distinct binding properties.
authors.affiliation: Department of Microbiology & Immunology, Key Immunopathology Laboratory of Guangdong Province, Shantou University Medical College, Shantou, PR China.
authors.forename: Heng
authors.initials: H
authors.lastname: Zhang
authors.forename: Weizhong
authors.initials: W
authors.lastname: Li
authors.forename: Gefei
authors.initials: G
authors.lastname: Wang
authors.forename: Yun
authors.initials: Y
authors.lastname: Su
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Xiaoxuan
authors.initials: X
authors.lastname: Chen
authors.forename: Yanxuan
authors.initials: Y
authors.lastname: Xu
authors.forename: Kangsheng
authors.initials: K
authors.lastname: Li
mesh_terms: D000818:Animals; D000076122:Disks Large Homolog 4 Protein; D047468:Immunoprecipitation; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011485:Protein Binding; D025941:Protein Interaction Mapping; D051381:Rats; D017207:Rats, Sprague-Dawley; D020798:Two-Hybrid System Techniques; D017361:Viral Nonstructural Proteins / Q000378:metabolism*
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; C085820:INS1 protein, influenza virus; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D017361:Viral Nonstructural Proteins; D009569:Nitric Oxide