Coxsackievirus and adenovirus receptor (CAR) (CAR)

The Coxsackievirus and adenovirus receptor (CAR), encoded by the CXADR gene, is a type I transmembrane glycoprotein and a member of the immunoglobulin superfamily [1, 6]. It is primarily localized at tight junctions in epithelial cells and intercalated discs in cardiac muscle, where it plays a crucial role in mediating homophilic and heterophilic cell-cell adhesion and maintaining tissue integrity [1, 12]. CAR is biologically significant as the essential entry point for group B coxsackieviruses and many adenovirus serotypes, facilitating their attachment and subsequent internalization into host cells [3, 11]. In clinical medicine, CAR is a pivotal target for adenoviral-based gene therapies and oncolytic viruses, such as Gendicine, which rely on its expression for efficient cellular transduction [2, 10]. However, its expression is often developmentally regulated and frequently downregulated in advanced cancers, which can impede the effectiveness of viral-mediated treatments [5, 9]. Current research focuses on using pharmacological agents like HDAC inhibitors to upregulate CAR expression in tumors or developing CAR-independent viral vectors to overcome these therapeutic barriers [2, 8]. Additionally, CAR's role in the heart makes it a factor in the pathogenesis of viral myocarditis and dilated cardiomyopathy [1, 9].

Other names

CXADRhCARCVB3-binding proteinCoxsackievirus B-adenovirus receptorCXADR Ig-like cell adhesion moleculeHCVADR

Facilitates viral attachment and internalization into host cells by binding to viral capsid proteins [1, 11]. In gene therapy, it serves as the primary entry portal for adenoviral vectors [2, 3]. Pharmacological induction of CAR expression by histone deacetylase (HDAC) inhibitors or phytoestrogens can enhance the uptake and efficacy of adenoviral-delivered genetic medicines [2, 10].