Identification of a surface glycoprotein on African green monkey kidney cells as a receptor for hepatitis A virus

Very little is known about the mechanism of cell entry of hepatitis A virus (HAV), and the identification of cellular receptors for this picornavirus has been elusive. Here we describe the molecular cloning of a cellular receptor for HAV using protective monoclonal antibodies raised against susceptible African green monkey kidney (AGMK) cells as probes, Monoclonal antibodies 190/4, 235/4 and 263/6, which reacted against similar epitopes, specifically protected AGMK cells against HAV infection by blocking the binding of HAV, Expression; cloning and nucleotide sequence analysis of the cDNA coding for epitope 190/4 revealed a novel mucin-like class I integral membrane glycoprotein of 451 amino acids, the HAV cellular receptor 1 (HAV cr-1). Immunofluorescence anal;sis indicated that mouse Ltk(-) cells transfected with HAV cr-1 cDNA gained Limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4, Our results demonstrate that the HAV cr-1 polypeptide is an attachment receptor for HAV and strongly suggest that it is also a functional receptor which mediates HAV infection, This report constitutes the first identification of a cellular receptor for HAV.