Cadherin-related family member 3, a childhood asthma susceptibility gene product, mediates rhinovirus C binding and replication
The rhinovirus C (RV-C) species was first identified in 2006 and is a major cause of acute respiratory illnesses in children and hospitalizations for exacerbations of asthma. In this study, we discovered that expression of human cadherin-related family member 3 (CDHR3), a transmembrane protein with yet unknown biological function, enables RV-C binding and replication in normally unsusceptible host cells. Intriguingly, we found that a coding SNP (rs6967330, C529Y) in CDHR3, previously linked to wheezing illnesses and hospitalizations for childhood asthma by genetic analysis, also mediates enhanced RV-C binding and increased progeny yields in vitro. Finally, using structural modeling, we identified potential binding sites in CDHR3 domains 1 and 2 interacting with viral capsid surface regions that are highly conserved among RV-C types.