A plant virus hijacks phosphatidylinositol-3,5-bisphosphate to escape autophagic degradation in its insect vector

Hosts can initiate macroautophagy/Autophagy as an Antiviral defense response, while viruses have developed multiple ways to evade the host autophagic degradation. However, little is known as to whether viruses can target lipids to subvert autophagic degradation. Here, we show that a low abundant signaling lipid, phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P₂), is required for rice black-streaked dwarf virus (RBSDV) to evade the autophagic degradation in the insect vector Laodelphax striatellus. RBSDV binds to PtdIns(3,5)P₂ and elevates its level through its main capsid protein P10, leading to inhibited Autophagy and promoted virus propagation. Furthermore, we show that PtdIns(3,5)P₂ inhibits the Autophagy pathway by preventing the fusion of autophagosomes and lysosomes through activation of TRPML (transient receptor potential cation channel, mucolipin), an effector of PtdIns(3,5)P₂. These findings uncover a strategy whereby a plant virus hijacks PtdIns(3,5)P₂ via its viral capsid protein to evade autophagic degradation and promote its survival in insects.