Influenza A virus NS1 protein binds p85β and activates phosphatidylinositol-3-kinase signaling

Hale et al. 10.1073/pnas.0606109103.

Supporting Figures

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Fig. 6. Specific inhibition of influenza A virus replication by the PI3K inhibitors LY294002 and wortmannin. Confluent Madin-Darby canine kidney (MDCK) monolayers were infected for 1 h with parainfluenza virus-5 (PIV-5; a) or wild-type influenza A/Puerto Rico/8/34 (PR8; b) at an MOI of 0.001 PFU per cell. After virus adsorption, monolayers were treated with DMSO (open circles) [solvent control], 25 mM LY303511 (filled circles) [LY294002 negative control], 25 mM LY294002 (open squares) [PI3K inhibitor], or 1 mM wortmannin (filled squares) [potent PI3K inhibitor]. Virus containing supernatants were harvested at regular times after infection, and titers were determined by plaque assay on Vero cells (PIV-5), or MDCK cells (PR8).

Supporting Figure 7

Fig. 7. Location of tyrosine-89 in the NS1 effector domain structure. Angled view of the NS1 effector domain dimer structure (Protein Data Bank ID code 2GX9) with the two monomers colored in blue and gold. The totally conserved tyrosine residue at position 89 (shown in red) is exposed in an apparent cleft at the interface between the two monomers, and is on the border of an extended chain region/helix. The methionine at position 93 (not highlighted) appears to be less well exposed, and may be a determinant of overall structure stability.