Coxsackievirus and adenovirus receptor (CAR) and integrin alpha-V beta-3 and integrin alpha-V beta-5 (CAR and integrins αvβ3/αvβ5)

The Coxsackievirus and Adenovirus Receptor (CAR) and integrins αvβ3 and αvβ5 function as a coordinated receptor system for the entry of various adenoviruses, particularly the widely used Adenovirus Serotype 5 (Ad5) (PubMed: 10482571). CAR, encoded by the CXADR gene, is a transmembrane protein of the immunoglobulin superfamily that mediates high-affinity viral attachment to the host cell surface (UniProt: P78310). Following attachment, the viral penton base protein interacts with integrins αvβ3 and αvβ5 via an RGD (Arg-Gly-Asp) motif, triggering clathrin-mediated endocytosis and subsequent endosomal escape (PubMed: 8343958). This dual-receptor mechanism is a critical determinant of viral tropism and is the primary pathway utilized by many gene therapy vectors and oncolytic viruses, such as Gendicine and Oncorine, to deliver therapeutic payloads (PubMed: 15133500). However, the clinical utility of these therapies is often limited by the downregulation of CAR in advanced, poorly differentiated tumors and the sequestration of viral particles in the liver, which expresses high levels of these receptors (PubMed: 11742419). Consequently, significant research is focused on engineering fiber-modified adenoviruses that can utilize alternative receptors or bypass CAR/integrin dependency to improve tumor-specific targeting and safety profiles.

Other names

CXADR and ITGAV:ITGB3/ITGAV:ITGB5Adenovirus receptor complexCAR/Integrin entry pathwayCoxsackie virus and adenovirus receptorIntegrin alpha-V beta-3Integrin alpha-V beta-5

Viral attachment to CAR followed by integrin-mediated endocytosis for gene delivery; competitive inhibition of integrin-extracellular matrix interactions.