Coxsackie and adenovirus receptor (CAR) (CAR)

The Coxsackie and adenovirus receptor (CAR), encoded by the CXADR gene, is a 46 kDa type I transmembrane glycoprotein and a member of the immunoglobulin superfamily (UniProt: P13569). It is primarily localized at the tight junctions of epithelial cells, where it functions as a cell adhesion molecule essential for maintaining tissue integrity and regulating paracellular permeability (PubMed: 10409711). CAR is clinically significant as the primary attachment receptor for group B coxsackieviruses and several adenovirus serotypes, most notably adenovirus serotype 5 (Ad5), which is the most common platform for gene therapy vectors (PubMed: 9036860). In oncology, CAR expression is often reduced in advanced tumors, which limits the efficacy of adenoviral-based therapies by hindering viral entry into malignant cells (PubMed: 11894015). Conversely, its high expression in the liver and other non-target tissues can lead to off-target sequestration and systemic toxicity, posing a challenge for the development of targeted viral delivery systems (PubMed: 12692558). Beyond its role in viral entry, CAR is involved in cardiac development and has been implicated in the pathogenesis of viral myocarditis (PubMed: 10358038). Therapeutic strategies often involve engineering adenoviral vectors to bypass CAR or using CAR-binding ligands to enhance delivery to CAR-deficient tumors.

Other names

CXADRhCARCoxsackievirus B-adenovirus receptorCVB receptor

The mechanism involves the high-affinity binding of the adenoviral fiber knob protein to the extracellular D1 domain of the Coxsackie and adenovirus receptor, which facilitates viral attachment to the host cell membrane, followed by integrin-mediated endocytosis (PubMed: 9036860).