Adenoviral entry receptors

Adenoviral entry receptors on endothelial cells are a group of cell surface proteins that facilitate the binding and internalization of adenoviruses into the vascular lining. The most prominent of these is the Coxsackievirus and adenovirus receptor (CAR), a member of the immunoglobulin superfamily that typically mediates cell-cell adhesion in tight junctions (Bergelson et al., Science, 1997; Tomko et al., PNAS, 1997). Other key receptors include CD46 (membrane cofactor protein), which is used by species B adenoviruses, and various integrins like alpha-V beta-3 and alpha-V beta-5 that serve as co-receptors for viral internalization via endocytosis (Gaggar et al., Nat Med, 2003; Wickham et al., Cell, 1993). In the context of endothelial cells, the expression and accessibility of these receptors are major determinants of the efficiency of adenoviral-based gene therapies and vaccines (Fechner et al., Gene Ther, 1999). For instance, CAR is often sequestered in tight junctions, which can limit the transduction of quiescent endothelial cells (Walters et al., J Biol Chem, 2002). These receptors are targeted by engineered adenoviral vectors, such as those used in cancer gene therapy (e.g., Gendicine) or COVID-19 vaccines (e.g., ChAdOx1-S), to deliver genetic material (Greig et al., J Virol, 2009). Understanding the distribution and function of these receptors is crucial for improving vector targeting and minimizing systemic side effects like vascular inflammation or off-target organ uptake (Zhang & Bergelson, J Virol, 2005; Greinacher et al., N Engl J Med, 2021).

Other names

Adenovirus receptorsCoxsackievirus and adenovirus receptorCARCD46Membrane cofactor proteinDesmoglein 2DSG2IntegrinsHeparan sulfate proteoglycansHSPGs

Viral attachment to primary receptors (e.g., CAR, CD46) followed by secondary interaction with integrins to trigger receptor-mediated endocytosis.