LAUSR

ABSTRACT Apoptosis and macroautophagy/autophagy, two important processes for host intracellular immunity against virus infection, are commonly deployed by arbovirus to promote its survival within an arthropod vector. Numerous studies have focused upon either apoptosis or autophagy initiated by arbovirus infection, with limited insight into the mechanisms underlying orchestration of vector immune tolerance to arbovirus. Using plant tomato yellow leaf curl virus (TYLCV)-infected whiteflies we identified a master regulator, PEBP4, that can be hijacked by the TYLCV coat protein (CP) and in turn synchronously activates apoptosis and autophagy. Once TYLCV invades a whitefly cell, the viral CP captures membrane-localized PEBP4, stabilizing PEBP4 association with RAF1. The triple complex blocks a MAPK phosphorylation cascade and triggers apoptosis. Simultaneously, virus CP competes for PEBP4 binding, promoting the disassociation of PEBP4 from ATG8 and initiating autophagy. The activation of autophagy degrades invasive TYLCV, whereas apoptosis increases the viral load by antagonizing autophagy. Amplification of autophagy intensity can eliminate arbovirus load but enhances whitefly fitness cost. In contrast, suppression of autophagy causes the viral load to exceed the vector capacity, which is also detrimental to whitefly survival. Thus, only mild intracellular immunity balanced by apoptosis and autophagy permits long-term coexistence between vectors and arboviruses. Abbreviations CP: coat protein; MAPK: mitogen-activated protein kinase; PEBP: phosphatidylethanolamine binding protein; TYLCV: tomato yellow leaf curl virus.