Adeno-associated virus receptor (AAVR) and terminal galactose-containing glycans (AAVR/Galactose)

The Adeno-associated virus receptor (AAVR), encoded by the KIAA0319L gene, is a type I transmembrane protein that serves as an essential entry receptor for a wide range of adeno-associated virus (AAV) serotypes [1]. It is characterized by five Polycystic Kidney Disease (PKD) domains, with PKD2 and PKD3 acting as the primary binding interfaces for the viral capsid [3]. For specific serotypes such as AAV9, the entry process is a multi-step mechanism that also requires primary attachment to cell-surface glycans with terminal galactose [2]. These glycans function as low-affinity attachment factors that concentrate the virus on the cell surface before it engages AAVR for high-affinity binding and subsequent internalization via clathrin-mediated endocytosis [2, 5]. This receptor-glycan complex is a critical determinant of the tissue tropism and transduction efficiency of AAV-based gene therapies, such as Onasemnogene abeparvovec, which utilizes the AAV9 capsid to target motor neurons [4]. Engineering the interaction between the viral capsid and these targets is a central focus in optimizing gene delivery vectors for various genetic and acquired diseases [5].

Other names

KIAA0319LKIAA0319-like proteinAAVRTerminal galactose glycansAAV9 receptor complex

The viral capsid first attaches to terminal galactose residues on cell-surface glycans, which facilitates subsequent high-affinity interaction with the PKD domains of the adeno-associated virus receptor (AAVR), triggering endocytosis and nuclear trafficking.