Many pathogens, including viruses, are orally acquired and infect cells within the gastrointestinal tract. To counter this, the gastrointestinal tract has evolved as a physical and immunological barrier. Moreover, the microflora within the intestinal tract plays a fundamental role in immunity; however, much remains unknown regarding the molecular mechanisms linking the microbiota to barrier immunity against enteric viruses. Using Drosophila as a model insect, we previously found that the ERK pathway controls innate immunity to oral infection within the intestinal epithelium. However, it remains unclear how ERK is activated to restrict infection. Here, we show that two signals are required to activate antiviral ERK signaling in the intestinal epithelium. One signal is dependent on the recognition of peptidoglycan from the commensals, including Acetobacter pomorum, which primes the NF-kB-dependent induction of the secreted factor Pvf2. However, the microbiota is not sufficient to induce; a second virus-dependent Cdk9-dependent signal is required for the production of Pvf2. We have screened a panel of transcription factors that are Cdk9-dependent and identified a transcription factor required for Pvf2 induction. These findings demonstrate that sensing of specific commensals primes inflammatory signaling required for epithelial antiviral responsiveness to restrict diverse enteric viral infections. Future studies are directed toward identifying additional antiviral pathways rapidly induced in the gut following oral challenge by performing RNA-seq.