Adeno-associated virus 2 (AAV2) receptor complex

The Adeno-associated virus 2 (AAV2) receptor complex is a multi-component system on the host cell surface that mediates the attachment and entry of AAV2 capsids. The primary attachment factor is heparan sulfate proteoglycan (HSPG), a ubiquitous glycan that captures the virus and concentrates it on the cell membrane (Summerford and Samulski, 1998). Following attachment, the virus interacts with the essential protein receptor, adeno-associated virus receptor (AAVR, also known as KIAA0319L), which is required for internalization and trafficking through the endosomal system (Pillay et al., 2016). Several co-receptors, including fibroblast growth factor receptor 1 (FGFR1), hepatocyte growth factor receptor (c-Met), and various integrins (e.g., alphaVbeta5 and alpha5beta1), further facilitate the entry process (Qing et al., 1999; Summerford et al., 1999; Kashiwakura et al., 2005). This receptor complex is a fundamental target for gene therapy, as AAV2 is the most extensively studied serotype and serves as the basis for numerous therapeutic vectors, such as voretigene neparvovec (Luxturna) for retinal dystrophy. Engineering the capsid to modulate its affinity for these receptors is a key strategy for improving the safety and efficacy of AAV-based medicines by enhancing tissue specificity and reducing off-target effects.

Other names

AAV2 entry factorsAAV2 attachment factorsAAV2 receptorsHSPG and AAVR complexKIAA0319L and HSPG

The AAV2 capsid binds to heparan sulfate proteoglycans (HSPG) for initial attachment, followed by interaction with the adeno-associated virus receptor (AAVR) and co-receptors (e.g., FGFR1, integrins) to trigger clathrin-mediated endocytosis and subsequent nuclear trafficking for genome delivery.