Species-specific immunity is induced when an effector protein from a specific pathogen strain is perceived by a cognate resistance (R) protein in the plant. In Arabidopsis, the R protein HRT, which confers resistance to turnip crinkle virus (TCV), is activated upon recognition of the TCV coat-protein (CP), a potent suppressor of host RNA silencing. Recognition by HRT does not require RNA silencing suppressor function of CP and is not associated with the accumulation of TCV-specific small-RNA. However, several components of the host RNA silencing pathway participate in HRT-mediated defense against TCV. For example, the double stranded RNA binding protein (DRB) 4 interacts with the plasma membrane localized HRT, and is required for its stability. Intriguingly, TCV infection promotes the cytosolic accumulation of the otherwise primarily nuclear DRB4, and this in turn inhibits HRT-DRB4 interaction. These data together with differential localization of DRB4 in plants inoculated with avirulent and virulent viruses, suggests that sub-cellular compartmentalization of DRB4 plays an important role in activation of HRT.