Coxsackievirus and adenovirus receptor and Integrins (CAR/Integrins)

The Coxsackievirus and adenovirus receptor (CAR), encoded by the CXADR gene, and alpha-v integrins (specifically alpha-v beta-3 and alpha-v beta-5) are cell surface proteins that cooperatively mediate the entry of subgroup C adenoviruses into host cells (UniProt P78310; Wickham et al., 1993). CAR serves as the primary attachment site for the viral fiber protein, while integrins act as co-receptors that facilitate internalization through the viral penton base's RGD motif (Bergelson et al., 1997). In the context of cancer, these molecules are critical for the efficacy of oncolytic virotherapies and gene delivery vectors like Gendicine and Oncorine. However, CAR expression is frequently downregulated in high-grade tumors and metastatic cells, a phenomenon often associated with epithelial-mesenchymal transition, which limits therapeutic uptake (Nalbantoglu et al., 1999). Conversely, integrins are often overexpressed in tumor neovasculature and stromal cells, making them attractive targets for tropism-modified viral vectors designed to enhance delivery to the tumor microenvironment.

Other names

CXADRCARhCARIntegrin alpha-VITGAVITGB3ITGB5Integrin alpha-v beta-3Integrin alpha-v beta-5

Viral attachment to CAR followed by integrin-mediated endocytosis (Wickham et al., 1993; Bergelson et al., 1997).