The PDZ-ligand and Src-homology type 3 domains of epidemic avian influenza virus NS1 protein modulate human Src kinase activity during viral infection

Laura Bavagnoli, William G. Dundon, Anna Garbelli, Bianca Zecchin, Adelaide Milani, Geetha Parakkal, Fausto Baldanti, Stefania Paolucci, Romain Volmer, Yizeng Tu, Chuanyue Wu, Ilaria Capua, Giovanni Maga

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Abstract

The Non-structural 1 (NS1) protein of avian influenza (AI) viruses is important for pathogenicity. Here, we identify a previously unrecognized tandem PDZ-ligand (TPL) domain in the extreme carboxy terminus of NS1 proteins from a subset of globally circulating AI viruses. By using protein arrays we have identified several human PDZ-cellular ligands of this novel domain, one of which is the RIL protein, a known regulator of the cellular tyrosine kinase Src. We found that the AI NS1 proteins bind and stimulate human Src tyrosine kinase, through their carboxy terminal Src homology type 3-binding (SHB) domain. The physical interaction between NS1 and Src and the ability of AI viruses to modulate the phosphorylation status of Src during the infection, were found to be influenced by the TPL arrangement. These results indicate the potential for novel host-pathogen interactions mediated by the TPL and SHB domains of AI NS1 protein.

Original languageEnglish
Article numbere27789
JournalPLoS One
Volume6
Issue number11
DOIs
Publication statusPublished - Nov 14 2011

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ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Bavagnoli, L., Dundon, W. G., Garbelli, A., Zecchin, B., Milani, A., Parakkal, G., Baldanti, F., Paolucci, S., Volmer, R., Tu, Y., Wu, C., Capua, I., & Maga, G. (2011). The PDZ-ligand and Src-homology type 3 domains of epidemic avian influenza virus NS1 protein modulate human Src kinase activity during viral infection. PLoS One, 6(11), [e27789]. https://doi.org/10.1371/journal.pone.0027789