Host cell adenoviral entry receptors and integrins (CAR and integrins)

Host cell adenoviral entry receptors and integrins are a group of cell surface proteins that facilitate the multi-step process of adenovirus infection [1]. The primary attachment is typically mediated by the Coxsackievirus and adenovirus receptor (CAR), which binds to the fiber knob of the viral capsid [1, 3]. Following attachment, the virus utilizes secondary receptors, primarily alpha-v beta-3 and alpha-v beta-5 integrins, to trigger internalization via clathrin-mediated endocytosis [2, 5]. This interaction is often mediated by an Arginine-Glycine-Aspartic acid (RGD) motif in the viral penton base [1, 2]. These receptors are critical targets in the development of oncolytic viruses and gene therapy vectors, such as Gendicine and Oncorine, where their expression levels determine the efficiency of viral transduction [4, 5]. Modulating these interactions is also a strategy for developing antiviral therapies to block adenovirus entry [4]. However, the widespread expression of these receptors can lead to off-target effects and safety concerns, such as liver sequestration, in therapeutic applications [1, 5].

Other names

Coxsackievirus and adenovirus receptorCXADRIntegrin alpha-V beta-3Integrin alpha-V beta-5Adenovirus attachment receptorAdenovirus internalization receptorVitronectin receptorAdenovirus receptors

Adenoviruses utilize a two-step entry mechanism involving initial high-affinity attachment to the Coxsackievirus and adenovirus receptor (CAR) via the viral fiber knob, followed by secondary interaction with alpha-v integrins (specifically alpha-v beta-3 and alpha-v beta-5) via the RGD motif in the penton base. This secondary interaction triggers clathrin-mediated endocytosis and subsequent viral internalization. Therapeutic strategies involve using these receptors as docking sites for gene therapy vectors or blocking them with antagonists to prevent viral infection.