Coxsackievirus and Adenovirus Receptor (CAR) and alpha-V integrins (CAR and alpha-V integrins)

The entry of the ChAdOx1 (Chimpanzee Adenovirus Oxford 1) vector into host cells is a coordinated process involving specific cell surface receptors. The primary attachment is mediated by the high-affinity binding of the viral fiber-knob protein to the Coxsackievirus and Adenovirus Receptor (CAR), a member of the immunoglobulin superfamily typically located in epithelial tight junctions (Baker et al., 2021). Following this initial docking, the vector undergoes internalization through the interaction of the Arg-Gly-Asp (RGD) motif in its penton base with host cell integrins, primarily alpha-V beta-3 and alpha-V beta-5 (Wickham et al., 1993). This secondary interaction triggers clathrin-mediated endocytosis, facilitating the delivery of the viral genome into the host cell nucleus for transgene expression. ChAdOx1 serves as the platform for several vaccines, most notably the AstraZeneca/Oxford COVID-19 vaccine (AZD1222). While these receptors are essential for vaccine efficacy, off-target interactions have been linked to rare adverse events. Specifically, the electronegative surface of the ChAdOx1 capsid can bind to the positively charged Platelet Factor 4 (PF4), a mechanism implicated in vaccine-induced immune thrombotic thrombocytopenia (VITT) (Greinacher et al., 2021). Additionally, recent research suggests that ChAdOx1 can directly engage activated platelet integrin alpha-IIb beta-3, potentially contributing to thrombotic risks under certain physiological conditions.

Other names

CXADRIntegrin alpha-V beta-3Integrin alpha-V beta-5AdV receptorsChAdOx1 entry receptorsHost cell adenovirus attachment receptors and integrins

The mechanism involves the high-affinity attachment of the viral fiber-knob protein to the Coxsackievirus and Adenovirus Receptor (CAR) followed by secondary interaction with alpha-V beta-3 and alpha-V beta-5 integrins to trigger clathrin-mediated endocytosis and transgene delivery.