Coxsackievirus and adenovirus receptor (CAR) (CAR)

The Coxsackievirus and adenovirus receptor (CAR), encoded by the CXADR gene, is a 46 kDa transmembrane glycoprotein and a member of the immunoglobulin superfamily that serves as a critical mediator of cell-cell adhesion and viral entry (UniProt, 2024). It is primarily localized at the tight junctions of epithelial cells and plays an essential role in the development of the heart and lymphatic system (Wikipedia, 2024). CAR is the primary receptor for group B coxsackieviruses and several adenovirus serotypes, most notably Adenovirus serotype 5 (Ad5), which is the most common vector used in gene therapy and oncolytic virotherapy (NIH, 2020). In the context of cancer, CAR expression is often downregulated in aggressive tumors, limiting the efficacy of Ad5-based treatments; consequently, related adenoviral entry receptors such as CD46 and desmoglein-2 (DSG2) are targeted by engineered chimeric viruses to improve tumor transduction (Frontiers in Oncology, 2024). The receptor's role in disease extends beyond viral infection, as it is involved in the regulation of the AKT signaling pathway and epithelial-mesenchymal transition in breast cancer (Cancer Research, 2019). Furthermore, CAR is a key determinant of the safety profile of adenoviral vectors, as its presence on hepatocytes leads to significant liver sequestration and potential hepatotoxicity following systemic administration (Amsterdam UMC, 2024). Therapeutic strategies often involve the use of HDAC inhibitors like Vorinostat to upregulate CAR expression or the development of retargeted viral vectors to bypass the requirement for CAR, addressing the challenges of low receptor density and off-target sequestration (PubMed, 2011).

Other names

CXADRhCARCVB3-binding proteinCoxsackie and adenovirus receptor-like membrane proteinAdenoviral entry receptorsCD46Desmoglein-2

Viral attachment and entry via fiber knob binding; transcriptional upregulation of receptor expression to enhance viral transduction