GAPDH Mediates Plant Reovirus-induced Incomplete Autophagy for Persistent Viral Infection in Leafhopper Vector

Macroautophagy/autophagy is a conserved mechanism launched by host organisms to fight against virus infection. Double-membraned autophagosomes in arthropod vectors can be remodeled by arboviruses to accommodate virions and facilitate persistent viral propagation, but the underlying mechanism is unknown. Rice gall dwarf virus (RGDV), a plant nonenveloped double-stranded RNA virus, induces the formation of virus-containing double-membraned autophagosomes to benefit persistent viral propagation in leafhopper vectors. In this study, it was found that the capsid protein P2 of RGDV alone induced autophagy. P2 specifically interacted with GAPDH (glyceraldehyde-3-phosphate dehydrogenase) and ATG4B both and . Furthermore, the GAPDH-ATG4B complex could be recruited to virus-induced autophagosomes. Silencing of or expression suppressed ATG8 lipidation, autophagosome formation, and efficient viral propagation. Thus, P2 could directly recruit the GAPDH-ATG4B complex to induce the formation of initial autophagosomes. Furthermore, such autophagosomes were modified to evade fusion with lysosomes for degradation, and thus could be persistently exploited by viruses to facilitate efficient propagation. GAPDH bound to ATG14 and inhibited the interaction of ATG14 with SNAP29, thereby preventing ATG14-SNARE proteins from mediating autophagosome-lysosome fusion. Taken together, these results highlight how RGDV activates GAPDH to initiate autophagosome formation and block autophagosome degradation, finally facilitating persistent viral propagation in insect vectors. The findings reveal a positive regulation of immune response in insect vectors during viral infection.