Parasitism to mutualism shift during a viral infection in Drosophila under thermal stress

Host–parasite interactions exist along a continuum from parasitism to mutualism, yet the environmental drivers governing transitions along this spectrum remain underexplored. Here we show that chronic thermal stress systematically attenuates virulence across multiple natural RNA viruses in Drosophila melanogaster and shifts persistent Nora virus infection into conditional mutualism, enhancing host lifespan, reproductive output, and behavioral performance without compromising viral persistence. Driven by host immunometabolic reprogramming and aging deceleration rather than viral genomic adaptation, this phenotypic switch demonstrates that thermal stress can invert the sign of biotic interactions. Our findings establish that persistent infections can expand host thermal reaction norms in animals, revealing how climate warming can fundamentally alter selection pressures and host–pathogen coevolutionary trajectories.