Human aminopeptidase N is a receptor for human coronavirus 229E

Human coronaviruses (HCV) in two serogroups represented by HCV-229E and HCV-OC43 are an important cause of upper respiratory tract infections. Here we report that human Aminopeptidase N, a cell-surface metalloprotease on intestinal, lung and kidney epithelial cells, is a receptor for human coronavirus strain HCV-229E, but not for HCV-OC43. A monoclonal antibody, RBS, blocked HCV-229E virus Infection of human lung fibroblasts, immunoprecipitated Aminopeptidase N and inhibited its enzymatic activity. HCV-229E-resistant murine fibroblasts became susceptible after transfection with complementary DNA encoding human Aminopeptidase N. By contrast, Infection of human cells with HCV-OC43 was not inhibited by antibody RBS and expression of Aminopeptidase N did not enhance HCV-OC43 replication in mouse cells. A mutant Aminopeptidase lacking the catalytic site of the Enzyme did not bind HCV-229E or RBS and did not render murine cells susceptible to HCV-229E Infection, suggesting that the virus-binding site may lie at or near the active site of the human Aminopeptidase molecule.