Coxsackievirus and Adenovirus Receptor (CXADR) and Integrins (CXADR/Integrins)

The Coxsackievirus and Adenovirus Receptor (CXADR), or CAR, is a transmembrane protein of the immunoglobulin superfamily that serves as the primary attachment site for many adenoviruses (Bergelson et al., 1997, Science). Following initial binding to CAR, the virus utilizes cell surface integrins, particularly alpha-V beta-3 and alpha-V beta-5, as co-receptors to facilitate internalization via receptor-mediated endocytosis (Wickham et al., 1993, Cell). In the context of ex vivo transduction, these molecules are the gatekeepers for delivering genetic material into target cells like dendritic cells (DCs). However, a significant challenge in DC-based immunotherapy is the naturally low expression of CAR on the surface of mature dendritic cells, which leads to poor transduction efficiency with standard Ad5 vectors (Rea et al., 1999, Journal of Virology). To circumvent this, researchers often engineer viral vectors to include RGD motifs that target integrins directly or use bispecific adapters to bridge the virus to other DC-specific receptors (Niederman et al., 2002, Human Gene Therapy). This receptor complex is therefore a critical focal point for optimizing gene transfer in the production of cancer vaccines and other cell-based therapies. Beyond viral entry, CAR and integrins play fundamental roles in cell adhesion and signaling within the immune system and various tissues (UniProt P19022). Understanding the density and distribution of these receptors on dendritic cells is essential for predicting the success of ex vivo genetic modification protocols.

Other names

CARhCARCXADRAdenovirus receptorIntegrin alpha-V beta-3Integrin alpha-V beta-5Vitronectin receptorITGAVITGB3

The Coxsackievirus and Adenovirus Receptor (CXADR) facilitates high-affinity viral attachment, while integrins alpha-V beta-3 and alpha-V beta-5 act as co-receptors to trigger viral internalization via clathrin-mediated endocytosis (Wickham et al., 1993, Cell).