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.
Department of Pathology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4799.
C L
CL
Yeager
R A
RA
Ashmun
R K
RK
Williams
C B
CB
Cardellichio
L H
LH
Shapiro
A T
AT
Look
K V
KV
Holmes
D000626:Aminopeptidases / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D000818:Animals; D000911:Antibodies, Monoclonal; D001665:Binding Sites; D018826:CD13 Antigens; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology; D003332:Coronaviridae / Q000502:physiology*; D004247:DNA / Q000235:genetics; D005347:Fibroblasts / Q000201:enzymology / Q000382:microbiology; D005434:Flow Cytometry; D006801:Humans; D007163:Immunosorbent Techniques; D008168:Lung / Q000201:enzymology / Q000382:microbiology; D051379:Mice; D011991:Receptors, Virus / Q000502:physiology*; D014162:Transfection
D000911:Antibodies, Monoclonal; D011991:Receptors, Virus; D004247:DNA; D000626:Aminopeptidases; D018826:CD13 Antigens