Natural self-attenuation of pathogenic viruses by deleting the silencing suppressor coding sequence for long-term plant-virus coexistence

Potyviridae is the largest family of plant-infecting RNA viruses. All members of the family (potyvirids) have positive-sense single-stranded RNA genomes, with polyprotein processing as the main expression strategy. The 5-proximal regions of their genomes encode two types of leader proteases: the serine protease P1 and the cysteine protease HCPro. However, their arrangement and sequence composition vary greatly among genera or even species. The leader proteases play multiple important roles in different potyvirid-host combinations, including RNA silencing suppression and virus transmission. Here, we report that viruses in the genus Arepavirus, which encode two HCPro leader proteases in tandem (HCPro1-HCPro2), can naturally lose the coding sequences for these two proteins during infection. Notably, this loss is associated with a shift in foliage symptoms from severe necrosis to mild chlorosis or even asymptomatic infections. Further analysis revealed that the deleted region is flanked by two short repeated sequences in the parental isolates, suggesting that recombination during virus replication likely drives this genomic deletion. Reverse genetic approaches confirmed that the loss of leader proteases weakens RNA silencing suppression and other critical functions. A field survey of areca palm trees displaying varied symptom severity identified a transitional stage in which full-length viruses and deletion mutants coexist in the same tree. Based on these findings, we propose a scenario in which full-length isolates drive robust infections and facilitate plant-to-plant transmission, eventually giving rise to leader protease-less variants that mitigate excessive damage to host trees, allowing long-term coexistence with the perennial host. To our knowledge, this is the first report of potyvirid self-attenuation via coding sequence loss. Author summaryPlant viruses typically persist throughout the lifespan of their host plants, employing multiple strategies to ensure long-term survival. This study reveals an unusual self-attenuation mechanism in which potyvirids, likely through recombination, discard a large genomic fragment containing the RNA silencing suppressor coding sequence. This deletion reduces viral pathogenicity, enabling a peaceful long-term virus-plant coexistence. Meanwhile, the attenuated viruses may function as natural vaccines, protecting plants from reinfection by the full-length pathogenic strains or related variants. These findings highlight a direct link between viral evolution and long-term coexistence, suggesting that such adaptations may promote mutual benefits. Understanding these dynamics could provide valuable insights into virus-host interactions and inspire new approaches to plant disease management.