Human adenovirus entry receptors (HAdV receptors)

Human adenovirus entry receptors are a heterogeneous group of cell surface proteins and glycans that mediate the multi-step process of adenovirus attachment and internalization. The primary attachment is typically facilitated by the viral fiber knob binding to receptors such as the coxsackievirus and adenovirus receptor (CAR), CD46 (membrane cofactor protein), or desmoglein 2 (DSG2), depending on the viral serotype. Subsequent to attachment, the viral penton base interacts with secondary receptors, primarily alpha-v integrins, to induce clathrin-mediated endocytosis and viral entry. These receptors are fundamental to the tissue tropism of the over 100 known human adenovirus serotypes, influencing the clinical presentation of infections ranging from respiratory disease to conjunctivitis. In therapeutic contexts, these receptors are the primary targets for engineering adenoviral vectors used in gene therapy and vaccine development, where retargeting strategies aim to bypass natural receptors to achieve cell-specific delivery. Understanding the distribution and function of these receptors is crucial for managing the safety and efficacy of adenovirus-based therapeutics, particularly regarding off-target effects and pre-existing host immunity.

Other names

Adenovirus receptorsCoxsackievirus and adenovirus receptor (CAR)Membrane cofactor protein (CD46)Desmoglein 2 (DSG2)Integrin alpha-v beta-3Integrin alpha-v beta-5Sialic acid receptorsHeparan sulfate proteoglycansAdenovirus attachment receptors

Viral attachment via fiber knob binding to primary receptors (CAR, CD46, or DSG2) followed by secondary interaction with integrins to trigger endocytosis.