Adeno-associated virus receptor (AAVR) and co-receptors (AAVR)

AAV9 cell-entry receptors and co-receptors are a group of host cell surface and intracellular molecules that facilitate the attachment, internalization, and trafficking of adeno-associated virus serotype 9 (AAV9). The primary attachment factor for AAV9 is terminal N-linked galactose, a unique glycan preference that distinguishes it from other serotypes and contributes to its broad tissue tropism, including its ability to cross the blood-brain barrier (Bell et al., 2011). Following attachment, the virus interacts with the essential proteinaceous receptor known as Adeno-associated virus receptor (AAVR, or KIAA0319L), which is required for the productive infection of most AAV serotypes by guiding the virus through the endosomal system (Pillay et al., 2016). Additionally, G protein-coupled receptor 108 (GPR108) has been identified as a critical entry factor localized to the trans-Golgi network that is necessary for AAV9 to escape the endocytic pathway and reach the nucleus (Meisen et al., 2020). These receptors are of paramount importance in biotechnology as AAV9 is a leading vector for gene therapy, notably used in the treatment of spinal muscular atrophy via the drug Onasemnogene abeparvovec (Zolgensma). Understanding the expression and distribution of these receptors is vital for predicting therapeutic efficacy, managing pre-existing immunity, and engineering next-generation vectors with improved tissue specificity.

Other names

KIAA0319LG protein-coupled receptor 108 (GPR108)Terminal N-linked galactose37/67-kDa laminin receptor (LamR)AAVR

Viral capsid binding and internalization