Adeno-associated virus receptor complex (AAVR)

Adeno-associated virus (AAV) capsid primary attachment receptors and entry co-receptors are a diverse set of cell surface molecules that mediate the multi-step process of AAV infection and cellular transduction. The process typically begins with the virus binding to primary attachment receptors, which are often glycans such as heparan sulfate proteoglycans (HSPG), sialic acid, or galactose, depending on the specific AAV serotype (Summerford & Samulski, 1998; Bell et al., 2011). This initial docking is followed by interaction with high-affinity proteinaceous co-receptors, most notably the Adeno-Associated Virus Receptor (AAVR, encoded by KIAA0319L), which is essential for the internalization and trafficking of most AAV serotypes (Pillay et al., 2016). Other co-receptors, including fibroblast growth factor receptor 1 (FGFR1) and the 37/67 kDa laminin receptor, further facilitate entry and intracellular signaling (Qing et al., 1999; Akache et al., 2006). In therapeutic contexts, these receptors are the primary determinants of the tropism and efficacy of AAV-based gene therapies. Drugs such as Onasemnogene abeparvovec and Voretigene neparvovec rely on these receptors to deliver genetic material to target tissues like the spinal cord or retina. Engineering capsid-receptor interactions is a key strategy for improving the precision of gene delivery and minimizing the impact of pre-existing host immunity (Drouin & Agbandje-McKenna, 2013).

Other names

AAVRKIAA0319LHeparan sulfate proteoglycanHSPGSialic acid receptorGalactose receptorFibroblast growth factor receptor 1 (FGFR1)Hepatocyte growth factor receptor (HGFR)Integrin alpha-V beta-537/67 kDa Laminin receptor

Viral capsid binding to primary attachment receptors (glycans) and entry co-receptors (proteins) facilitates receptor-mediated endocytosis and intracellular trafficking to the nucleus for gene delivery.