FIG. 8.

Illustration of the virus and TLR3 activated signaling pathways, and the points at which the Nipah virus V and W proteins are predicted to exert their inhibitory activity. Stimulation of TLR3 by dsRNA activates a signaling cascade that is mediated by the adapter, TRIF, and results in activation of the kinase TBK-1. TBK-1 phosphorylates the transcription factor, IRF3, leading to activation of IRF3-responsive promoters. The Nipah virus W protein targets a nuclear component of this signaling pathway that results in the loss of phosphorylated IRF3. Virus infection also results in the activation of IRF3-responsive promoters, and the nuclear portion of this pathway is probably shared with that of the TLR3 pathway, so the W protein is also able to inhibit virus-activated signaling. The upstream signaling events in the virus pathway are distinct from those in the TLR3 pathway in that signaling is mediated predominantly by IKKɛ (thick arrow), although a minor contribution of TBK-1 cannot be excluded (broken arrow). The Nipah virus V protein is only able to prevent gene activation in response to IKKɛ and therefore is restricted to blocking the virus pathway, presumably downstream of IKKɛ.