Vacuoles are the largest compartments in plant cells and are involved in plant development and response to abiotic and biotic stresses. Vacuolar acidification is essential for vacuoles in various physiological functions. However, its role in plant defense, and whether and how pathogens affect vacuolar acidification to promote infection have never been reported. In this autophagy punctum, we discuss our recent findings about how plant viruses suppress vacuolar acidification and the degradation of autophagic bodies by directly interacting with a component of the V-ATPase to promote virus infection.