Coxsackie and adenovirus receptor (CAR)

The Coxsackie and adenovirus receptor (CAR), encoded by the CXADR gene, is a type I transmembrane glycoprotein and a member of the immunoglobulin superfamily [5, 14]. It is primarily localized within the tight junctions of epithelial cells, where it plays a crucial role in cell-cell adhesion and the regulation of paracellular permeability [4, 5]. Beyond its physiological role, CAR is the primary docking site for group B coxsackieviruses and many adenoviruses, including the ChAdOx1 vector used in the AstraZeneca COVID-19 vaccine [1, 2]. In the context of ChAdOx1, CAR facilitates the initial attachment of the viral vector to the host cell membrane via the fiber knob protein, which is a prerequisite for subsequent internalization and expression of the encoded antigen [1, 3]. While CAR is widely expressed in various tissues, its downregulation in certain advanced cancers can limit the efficacy of adenovirus-based oncolytic therapies and gene delivery systems [14, 17]. Recent research has also highlighted the role of the ChAdOx1 vector's interaction with CAR and other proteins like Platelet Factor 4 (PF4) in the pathogenesis of rare side effects such as vaccine-induced immune thrombotic thrombocytopenia (VITT) [1, 2, 9].

Other names

CXADRCoxsackievirus and adenovirus receptorhCARHCVADRCoxsackievirus B-adenovirus receptor

The ChAdOx1 adenoviral vector utilizes its fiber knob protein to bind with high affinity to the D1 domain of the Coxsackie and adenovirus receptor (CAR) on the host cell surface [1, 2]. This interaction serves as the primary docking mechanism, facilitating the subsequent internalization of the viral vector through receptor-mediated endocytosis [12, 13]. Once inside the cell, the vector releases its genetic payload into the nucleus for transcription and translation of the target antigen [6, 18].