Influenza virus non-structural protein 1 (NS1) disrupts interferon signaling.

Type I interferons (IFNs) function as the first line of defense against viral infections by modulating cell growth, establishing an antiviral state and influencing the activation of various immune cells. Viruses such as influenza have developed mechanisms to evade this defense mechanism and during infection with influenza A viruses, the non-structural protein 1 (NS1) encoded by the virus genome suppresses induction of IFNs-α/β. Here we show that expression of avian H5N1 NS1 in HeLa cells leads to a block in IFN signaling.

Interferon-inducible Stat2 activation of JUND and CLDN4: mediators of IFN responses.

Signal transducer and activator of transcription 2 (Stat2) is a critical signaling protein involved in mediating interferon-alpha/beta (IFN-alpha/beta) responses. Using site-directed mutagenesis in conjunction with gene microarray and biologic studies, we have previously demonstrated that in addition to Stat2 functioning as a transactivator of transcription of a subset of IFN-inducible genes (ISG), Stat2-DNA binding mediates the transcriptional activation of other ISGs required for IFN-inducible antiviral and growth inhibitory responses. Among these, two candidate genes identified were Jun-D (JUND) and claudin-4 (CLDN4).