Coxsackievirus and adenovirus receptor and Desmoglein-2 (CAR/DSG2)

The Coxsackievirus and adenovirus receptor (CAR) and Desmoglein-2 (DSG2) are distinct cell surface proteins that serve as the primary entry points for various adenovirus serotypes. CAR, a member of the immunoglobulin superfamily, is typically localized within tight junctions and is the high-affinity receptor for species C adenoviruses like Ad5 (UniProt P78310). DSG2, a cadherin family member found in desmosomes, serves as the receptor for species B adenoviruses such as Ad3, Ad7, and Ad11 (UniProt Q14126; Wang et al., 2011, Nature Medicine). In oncology, these receptors are exploited by oncolytic viruses like Enadenotucirev to selectively infect and destroy malignant cells. Additionally, the interaction between DSG2 and specialized proteins like JO-1 is used to transiently open tumor cell junctions, facilitating the penetration of large therapeutic molecules like monoclonal antibodies into solid tumors (Richter et al., 2012, Science Translational Medicine). Monitoring the expression of these receptors is vital for predicting the efficacy of adenoviral-based therapies and managing potential off-target effects in healthy tissues where these proteins are also expressed.

Other names

CXADRDSG2hCARCDHF5Coxsackie virus and adenovirus receptorDesmoglein-2

Acts as a primary docking site for adenoviral attachment and internalization via endocytosis; JO-1 binding to DSG2 triggers transient remodeling of intercellular junctions to increase paracellular permeability and drug penetration.