Host determinants of adeno-associated viral vector entry

Abstract

Viral vectors based on adeno-associated virus (AAV) are leading candidates for therapeutic gene delivery. Understanding rate-limiting steps in the entry of AAV vectors may be used in a rational approach to improve efficiency and specificity of transduction. This review describes our current understanding of AAV entry, a key step during infection. We discuss the identity and functions of AAV receptors and attachment factors, including the recently discovered multi-serotype receptor AAVR. We further provide an overview of other host factors that act during the trafficking stage of AAV vector transduction. In particular, we focus on cellular protein complexes associated with retrograde transport from endosomes to the trans-Golgi network. The novel insights in AAV-host interactions facilitated by technological advances in genetic screening approaches provide a greater depth in our understanding how AAV vectors exploit host factors to deliver its genetic cargo to the nucleus.

Figure 1

Schematic representation of the possible roles of AAVR in the AAV life cycle - (i) AAV binds to HSPG, allowing subsequent interaction with AAVR at the cell surface, which facilitates entry into the endosomal network; (ii) AAVR interacts with AAV in the endosomal system and facilitates trafficking to the trans-Golgi. (iii) Once in the trans-Golgi network, AAVR facilitates AAV escape into the cytoplasm.