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 pic ornavirus has been elusive. Here we describe the molecular cloning of a cellular receptor for HAV using protective monoclonal antibodies rai sed against susceptible African green monkey kidney (AGMK) cells as pr obes, Monoclonal antibodies 190/4, 235/4 and 263/6, which reacted agai nst similar epitopes, specifically protected AGMK cells against HAV in fection by blocking the binding of HAV, Expression; cloning and nucleo tide 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 t reatment with monoclonal antibody 190/4, Our results demonstrate that the HAV cr-1 polypeptide is an attachment receptor for HAV and strongl y suggest that it is also a functional receptor which mediates HAV inf ection, This report constitutes the first identification of a cellular receptor for HAV.