Adeno-associated virus receptor (AAVR) and N-linked galactose-containing glycans (AAVR/Gal-glycans)

Adeno-associated virus receptor (AAVR), also known as KIAA0319L, is a type I transmembrane protein that serves as an essential entry receptor for a wide range of adeno-associated virus (AAV) serotypes (Pillay et al., 2016, Nature). It facilitates the transition of the virus from the plasma membrane to the nucleus through a series of endocytic and trafficking events. For specific serotypes such as AAV9, the entry process also requires cell-surface N-linked glycans with terminal galactose residues, which act as primary attachment factors to concentrate the virus on the cell surface (Shen et al., 2011, J. Biol. Chem.). This dual-receptor mechanism is a critical determinant of the viral tropism and transduction efficiency observed in clinical gene therapy. Drugs such as onasemnogene abeparvovec (Zolgensma) utilize this pathway, specifically leveraging the AAV9 capsid's affinity for galactose and AAVR to deliver therapeutic genes to motor neurons (Mendell et al., 2017, NEJM). Understanding the distribution and density of both AAVR and these specific glycans is vital for optimizing vector design and predicting patient responses to AAV-based treatments.

Other names

KIAA0319LKIAA0319-like proteinAAV receptorTerminal galactose glycansAAV9 receptor complexN-linked galactose

AAV9 capsids first bind to terminal galactose residues on cell-surface N-linked glycans to facilitate cell attachment; subsequently, the virus engages the Adeno-associated virus receptor (AAVR) for endocytosis and intracellular trafficking to the nucleus.