Desmoglein 2 is a receptor for adenovirus serotypes 3, 7, 11 and 14

Abstract

A subset of series B adenoviruses binds epithelial cells via a previously unknown receptor. Wang et al. now identify this receptor as desmoglein-2 (DSG-2), which has a role in intercellular adhesion. Binding of group B Ad3 to DSG-2 triggered an epithelial to mesenchymal transition, opened intercellular junctions and increased access to junction-localized proteins, which together may contribute to the spread of these viruses though epithelial tissues. We have identified desmoglein-2 (DSG-2) as the primary high-affinity receptor used by adenoviruses Ad3, Ad7, Ad11 and Ad14. These serotypes represent key human pathogens causing respiratory and urinary tract infections. In epithelial cells, adenovirus binding of DSG-2 triggers events reminiscent of epithelial-to-mesenchymal transition, leading to transient opening of intercellular junctions. This opening improves access to receptors, for example, CD46 and Her2/neu, that are trapped in intercellular junctions. In addition to complete virions, dodecahedral particles (PtDds), formed by excess amounts of viral capsid proteins, penton base and fiber during viral replication, can trigger DSG-2–mediated opening of intercellular junctions as shown by studies with recombinant Ad3 PtDds. Our findings shed light on adenovirus biology and pathogenesis and may have implications for cancer therapy.