Cell-surface receptors and glycoconjugates used by the AAV capsid

The cell-surface receptors and glycoconjugates used by the adeno-associated virus (AAV) capsid are a heterogeneous group of host factors that mediate the complex process of viral entry. This process typically begins with a primary attachment to cell-surface glycans, which serve as attachment factors to concentrate the virus on the cell membrane. Specific glycans are utilized by different AAV serotypes: heparan sulfate proteoglycans (HSPG) for AAV2, AAV3, and AAV6; sialic acid for AAV1, AAV4, AAV5, and AAV6; and galactose for AAV9 (Asokan et al., 2012, Molecular Therapy). Following attachment, the virus engages essential protein receptors for internalization, most notably the Adeno-associated virus receptor (AAVR, also known as KIAA0319L), which is a universal entry factor for most AAV serotypes (Pillay et al., 2016, Nature). Other critical factors include GPR108 and various co-receptors such as FGFR1, integrins, and the laminin receptor (Dudek et al., 2020, Molecular Therapy). These interactions are the primary determinants of AAV tissue tropism and are exploited in the design of AAV-based gene therapies to deliver genetic material to specific target tissues. Understanding the molecular basis of these interactions is crucial for optimizing vector efficiency and overcoming challenges such as pre-existing immunity and off-target transduction (NIH, 2021).

Other names

AAV entry factorsAAV attachment factorsAdeno-associated virus receptorAAVRKIAA0319LHeparan sulfate proteoglycanHSPGSialic acidGalactoseGPR108

Mediation of viral attachment and entry into host cells via receptor-mediated endocytosis.