Specific and efficient translation inhibition–transcription activation resistance module against viruses in plants

Positive-sense RNA viruses using subgenomic RNAs (sgRNAs) cause severe crop losses, yet this conserved feature has rarely been exploited for antiviral engineering. Here, we constructed a virus-activated synthetic immune circuit, wherein viral sgRNA production drives host defense responses via a translation inhibition–transcription activation (TI-TA) module. An optimized translational repression element (dsBC) minimized basal expression while enabling virus-specific activation of resistance-inducing proteins (RIPs) by cognate viral sgRNA promoters. This circuit functioned against three major sgRNA-producing viruses—pepino mosaic virus (PepMV), tobacco mosaic virus (TMV), and cucumber mosaic virus (CMV)—in Nicotiana benthamiana , tomato, and Arabidopsis thaliana , with cross-resistance to related viruses. RIP expression was strictly triggered by viral infection, conferring robust resistance without detectable growth penalties. This programmable strategy provides a versatile platform for engineering resistance against diverse sgRNA-producing RNA viruses and offers a conceptual framework for developing synthetic antiviral immunity in plants.