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 single-stranded positive-sense RNA genomes, with polyprotein processing as the expression strategy. The 5'-proximal regions of all potyvirids, except bymoviruses, 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.