Non-canonical induction of autophagy increases adeno-associated virus type 2 (AAV2) transduction efficiency

Abstract

Adeno-associated virus (AAV) serotypes infect a wide range of cell types, making this member of the parvovirus family a versatile tool in gene therapy. Infection as well as transduction is set in motion by means of specific receptors in conjunction with trafficking pathways, particularly endocytosis, a main cell entry pathway of non-enveloped viruses. Here, we report that efficacy of transduction is enhanced upon treating cells with hyperosmotic sucrose, a known blocker of clathrin-mediated endocytosis, through the non-canonical induction of autophagy. This mechanism of autophagy induction, however, is different from the previously reported AAV2-mediated induction of autophagy, which relies on a canonical, phosphoinositide 3-kinase class III (PI3K-III) complex-dependent pathway and appears to be dependent on the virus intrinsic secreted phospholipase A2 (sPLA2) domain, particularly its catalytic center activity.