Papaya ringspot virus type P (PRSV-P) is one of the most devastating diseases of Carica papaya (papaya). No resistance has been reported within the cultivated genome; however, resistance exists within wild related species in genus Vasconcellea. Since 1998, breeding strategies have focussed on transferring resistance alleles from V. pubescens and V. quercifolia into V. parviflora and papaya. Previously, the V. pubescens resistance was characterised at the prv1 locus, located in close proximity to two kinase (VP_STK1 and VP_STK2) and one leucine rich repeat (VP_LRR) genes. Subsequently, the functional response of these genes in V. quercifolia, and potential differential response among wild and cultivated genomes, was assessed by transcriptional profiling following PRSV-P inoculation. Initially, the resistance response within V. quercifolia was confirmed through a controlled inoculation bioassay. Following inoculation with an equal viral titer, the viral coat protein (CP) level was significantly up regulated in C. papaya compared to non-significant CP expression in V. quercifolia from 20 to 30 days after inoculation (DAI). Putative resistance genes were identified in V. quercifolia using RACE-PCR and named VQ_STK2, VQ_STK2.1 and VQ_LRR. VQ_STK2 was significantly and differentially up-regulated in V. quercifolia between 0.15 and 1.5 fold from 5 to 30 DAI. In contrast, VQ_STK2 was significantly reduced after papaya plants were inoculated to the lowest point of down-regulation of 0.6 fold expression at 20 DAI. This indicated that STK2 may have a role in the sustained viral defence mechanism present in V. quercifolia and will be a target for further functional validation.