FIG. 8.

Model for continued defect in IRF-3-deficient BMDCs. Postattachment, HSV-1 infection is recognized through an unknown sensor mechanism that leads to activation of IRF-3. The early recognition pathway mediates the production of type I IFN- and IRF-3-dependent ISGs, leading to the control of HSV-1 replication via the type I IFN cascade. However, pretreatment with IFN does not restore HSV-1 replication in IRF-3^−/− BMDCs to WT levels. The continued defect is potentially due to three, nonexclusive mechanisms outlined in white squares: defective IFN amplification, defective antiviral trigger signaling, and IRF-3-dependent gene synergy with the antiviral response. One or more of these mechanisms leads to continued defect in the control of HSV-1 replication in IRF-3^−/− BMDCs compared to WT BMDCs after IFN treatment.