The type I interferon (IFN)-mediated host innate immune response is the primary defense against viral infection through the production of type I IFNs (IFNα/β), which bind to receptors on infected and neighbouring cells to activate intracellular signal transducers and activators of transcription 1 and 2 (STAT1 and 2) proteins leading to the establishment of a potent antiviral state. Subversion of the IFN system is thus a key component of pathogenic viral infection and is mediated by virus-encoded IFN-antagonist proteins. Immune evasion by the lethal human pathogen rabies virus (RABV) depends on specific targeting of cytokine-activated STAT1/2 by the IFN-antagonist P-protein, but targeting of other STATs has not been investigated. We have previously shown that P-protein is also able to target STAT3, which is activated both by IFNs and by IL6-family cytokines such as oncostatin M (OSM) through Gp130-dependent signalling. Importantly, this interaction was prevented by deletion of P-protein’s C-terminal 30 residues, which is known to abrogate STAT1/2 interaction. Using a combination of quantitative confocal microscopic analysis and immune signalling assays, we found that a high affinity P-STAT3 interaction is dependent on the presence of STAT1, indicating that the P-protein may target specific STAT complexes. Furthermore, since the P-STAT1 interaction has been shown to be critical for rabies disease, we aim to identify sites that are crucial for the P-STAT1 interaction using a combination of cell-based signalling assays and NMR-based structural biology and fragment screening approaches, to identify potential targets for the development of new vaccines as well as therapeutic approaches to combat currently incurable rabies disease.