Heparan sulfate proteoglycan and Adeno-associated virus serotype 2 co-receptors (HSPG/AAV2 co-receptors)

Heparan sulfate proteoglycans (HSPGs) serve as the primary attachment receptors for Adeno-associated virus serotype 2 (AAV2), facilitating the initial docking of the viral capsid onto the host cell surface [Summerford & Samulski, 1998, J Virol]. Following attachment, AAV2 utilizes several co-receptors to mediate entry and intracellular trafficking, most notably the Adeno-associated virus receptor (AAVR, also known as KIAA0319L), which is essential for endosomal escape and successful infection [Pillay et al., 2016, Nature]. Other identified co-receptors include Fibroblast Growth Factor Receptor 1 (FGFR1), Hepatocyte Growth Factor Receptor (c-Met), and alpha-V beta-5 integrins, which assist in internalization and signaling [Qing et al., 1999, Nat Med; Summerford et al., 1999, Nat Med]. In clinical applications, these receptors are the primary determinants of the tissue tropism and transduction efficiency of AAV2-based gene therapies, such as Voretigene neparvovec [Luxturna Prescribing Information]. Therapeutic challenges include the broad expression of HSPGs leading to non-specific distribution and the presence of pre-existing neutralizing antibodies that block receptor binding. Understanding the interplay between HSPG and these co-receptors is vital for engineering next-generation AAV vectors with improved specificity and reduced immunogenicity.

Other names

HSPGAAV2 receptorsAdeno-associated virus receptorAAVRKIAA0319LFibroblast growth factor receptor 1FGFR1Hepatocyte growth factor receptorMETIntegrin alpha-V beta-5Integrin alpha-V beta-1

Viral attachment to cell surface glycans followed by receptor-mediated endocytosis and intracellular trafficking.