Influenza virus-induced AP-1-dependent gene expression requires activationof the JNK signaling pathway (vol 276, pg 10990, 2001)

Influenza A virus infection of cells results in the induction of a variety of antiviral cytokines, including those that are regulated by transcription factors of the activating protein-1 (AP-1) family. Here we show that influ enza virus infection induces AP-1-dependent gene expression in productively infected cells but not in cells that do not support viral replication. Amo ng the AP-1 factors identified to bind to their cognate DNA element during viral infections of Madin-Darby canine kidney and U937 cells are those that are regulated via phosphorylation by JNKs. Accordingly, we observed that i nduction of AP-1-dependent gene expression correlates with a strong activat ion of JNK in permissive cells, which appears to be caused by viral RNA acc umulation during replication. Blockade of JNK signaling at several levels o f the cascade by transient expression of dominant negative kinase mutants a nd inhibitory proteins resulted in inhibition of virus-induced JNK activati on, reduced AP-1 activity, and impaired transactivation of the IFN-P promot er. Virus yields from transfected and infected cells in which JNK signaling was inhibited were higher compared with the levels from control cells. The refore, we conclude that virus-induced activation of JNK and AP-1 is part o f the innate antiviral response of the cell.