Autophagic degradation of the Cucumber mosaic virus virulence factor 2b balances antiviral RNA silencing with proviral plant fitness and virus seed transmission

Autophagy is a conserved intracellular degradation pathway that has recently emerged as an integral part of plant responses to virus infection. The elucidated mechanisms of autophagy range from the selective degradation of viral components to a more general attenuation of disease symptoms. In addition, several viruses are able to manipulate the autophagy machinery and counteract autophagy-dependent resistance. Despite these findings, the complex interplay of autophagy activities, viral pathogenicity factors, and host defence pathways in disease development remains poorly understood. In the current study, we analysed the interaction between autophagy and Cucumber mosaic virus (CMV) in Arabidopsis thaliana. We show that autophagy is induced during CMV infection and promotes the turnover of the major CMV virulence protein and RNA silencing suppressor 2b. Intriguingly, 2b itself dampens plant autophagy. In accordance with 2b degradation, we found that autophagy provides resistance against CMV by reducing viral RNA accumulation in an RNA silencing-dependent manner. Moreover, autophagy and RNA silencing pathways contribute to plant longevity and fecundity of CMV infected plants in an additive manner, uncoupling it from resistance. In addition to reduced fecundity, autophagy-deficient plants also failed to support seed transmission of the virus. We propose that autophagy attenuates CMV virulence via 2b degradation and thereby increases both plant and virus fitness with a trade-off penalty arising from increased RNA silencing-mediated resistance.Author summaryThe capacity of plants to fight pathogenic viruses in order to survive and minimize damage relies on profound cellular reprogramming events. These include the synthesis of new as well as the degradation of pre-existing cellular components, together shifting cellular homeostasis towards a better tolerance of disease and fortification of antiviral defence mechanisms. Autophagy is a prominent and highly conserved cellular degradation pathway that supports plant stress resilience. Autophagy functions vary broadly and range from rather unspecific renewal of cytoplasm to highly selective degradation of a wide collection of specific substrates. Autophagy is well established to be involved during virus infections in animals, and its importance has also recently emerged in virus diseases of plants. However, we are still far from a comprehensive understanding of the complexity of autophagy activities in host-virus interactions and how autophagy pathway engineering could be applied against viruses. Here, we have analyzed one of the traditional model plant viruses, Cucumber mosaic virus (CMV), and its interactions with autophagy. Our study revealed that autophagy is tightly integrated into CMV disease, influencing processes from plant health to CMV epidemiology.