Virus mediated SOCS-3 gene induction at early stages of infection ( Figures 4A, 4C and S1A) appeared to occur concomitant with an immediate and strong induction of IFNb ( Figures 4B and S1D) . This prompted us to analyze whether SOCS-3 transcription might be induced due to an auto-or paracrine action of IFNb expressed during infection. A549 cells were stimulated with IFNb for different time points and SOCS-3 gene induction was measured by qRT-PCR ( Figure 4D ). As a control we monitored expression of 29, 59oligoadenylate synthetase (OAS1) and MxA, genes that are typically induced by IFNb. While OAS1 and MxA mRNAs were readily upregulated upon IFNb treatment SOCS-3 mRNA was not significantly elevated ( Figure 4D ). Similar results were obtained from HUVEC stimulated with IFNb ( Figure S1E ). To further confirm these results we knocked down the IFNAR in A549-cells by an siRNA approach. Although the knock down was efficient and leads to more than 60% inhibition of IFNb induced STAT1 phosphorylation ( Figure 4E ), the induction of SOCS-3 expression was not impaired ( Figure 4F ). SOCS-3 levels in the knock down cells were similar compared to wild type cells and even higher than in the vector control ( Figure 4F ). These results are consistent with data gained from previous experiments in Vero cells ( Figure 1E ) and indicate that neither induction of SOCS-3 mRNA nor inhibition of STAT phosphorylation is dependent on virus-induced type I IFN expression.