PS2-80 Cloning, expression and characterization of chicken IFNλ

The innate cellular response to virus particle entry involves the induction of an antiviral state that inhibits viral replication. This signaling pathway requires the transcription factor interferon (IFN) regulatory factor 3 (IRF-3) for the expression of a subset of IFN stimulated genes (ISGs) that are sufficient to limit the replication and spread of a subsequent viral challenge. This signaling pathway occurs in the absence of viral replication and requires viral entry; however, many of the classical receptors that initiate an antiviral cascade are not required. Here, we implicate reactive oxygen species (ROS) as an inducer of this signaling pathway. We show that entry of different enveloped virus particles induces ROS, leading to IRF-3 activation and ISG production. Furthermore, we show that ROS inhibition via two distinct chemical inhibitors is sufficient to inhibit IRF-3 activation in response to virus particle entry. Together, our data suggest a role for ROS in the activation of IRF-3 following virus particle entry and subsequent induction of an IFN-independent antiviral state.