Cotton leaf curl Multan virus βC1 Protein Induces Autophagy by Disrupting the Interaction of Autophagy-Related Protein 3 with Glyceraldehyde-3-Phosphate Dehydrogenases[OPEN]

Viral beta C1 protein disrupts the ATG3-GAPC interaction and thereby induces autophagy. Autophagy plays an important role in plant-pathogen interactions. Several pathogens including viruses induce autophagy in plants, but the underpinning mechanism remains largely unclear. Furthermore, in virus-plant interactions, viral factor(s) that induce autophagy have yet to be identified. Here, we report that the beta C1 protein of Cotton leaf curl Multan betasatellite (CLCuMuB) interacts with cytosolic glyceraldehyde-3-phosphate dehydrogenase (GAPC), a negative autophagic regulator, to induce autophagy in Nicotiana benthamiana. CLCuMuB beta C1 bound to GAPCs and disrupted the interaction between GAPCs and autophagy-related protein 3 (ATG3). A mutant beta C1 protein (beta C1(3A)) in which I45, Y48, and I53 were all substituted with Ala (A), had a dramatically reduced binding capacity with GAPCs, failed to disrupt the GAPCs-ATG3 interactions and failed to induce autophagy. Furthermore, mutant virus carrying beta C1(3A) showed increased symptoms and viral DNA accumulation associated with decreased autophagy in plants. These results suggest that CLCuMuB beta C1 activates autophagy by disrupting GAPCs-ATG3 interactions.