Decrease of STAT phosphorylation might also be due to the action of virus-induced phosphatases. On the one hand these enzymes may cause direct dephosphorylation of STAT proteins. On the other hand phosphatases could act via an indirect mechanism by dephosphorylation and inactivation of JAKs resulting in an attenuated phosphorylation of STATs. Several protein tyrosine phosphatases (PTPs) are known to mediate dephosphorylation of both, JAKs and STATs [41] . In order to investigate whether influenza A virus activates phosphatases that subsequently target JAKs or STATs, we treated infected or uninfected A549 cells with the well-known tyrosine phosphatase inhibitor sodium vanadate [42, 43] . Uninfected cells or cells infected with PR8 for 10 h were incubated with increasing amounts of this compound 10 min prior to stimulation with IFNb. This time point of infection was chosen since we observed considerable inhibition of IFN-induced STAT1 phosphorylation in the course of infection ( Figures 1A and 1E ). Increasing concentrations of vanadate lead to a gradual shift of the steady state balance of phosphorylation/dephosphorylation. Accordingly, a gradual increase of STAT1 phosphorylation was observed that was similar in both infected and uninfected cells, albeit starting from different basal levels of phospho-STAT1 ( Figures 3A and B ). This is illustrated by an almost identical slope of the regression line in the graphical analysis of the band intensities of the IFNb stimulated samples ( Figure 3B ). If the blockade of IFNb-induced STAT1 phosphorylation would be mediated by specific virus-activated phosphatases, a much steeper slope for vanadate-treated infected cells would be expected. However, the result in Figure 3B indicates that the virus-induced suppression of phosphorylation is not compensated by phosphatase inhibition and consequently no virusactivated phosphatase appears to be involved. In support of these data, phosphatase assays revealed that the overall activity of tyrosine phosphatases in infected cells was not elevated compared to uninfected cells. This is indicated by constant levels of free phosphates released from two different phospho-peptides that represent common tyrosine phosphatase substrates ( Figure 3C ). Thus, involvement of phosphatases in influenza virus-induced alteration of STAT1 phosphorylation can be greatly ruled out.