Identification of a Surface Glycoprotein on African Green Monkey Kidney Cells as a Receptor for Hepatitis A Virus

EMBO J. 1996 Aug 15;15(16):4282-96.

Abstract

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 (HAVcr-1). Immunofluorescence analysis indicated that mouse Ltk- cells transfected with HAVcr-1 cDNA gained limited susceptibility to HAV infection, which was blocked by treatment with monoclonal antibody 190/4. Our results demonstrate that the HAVcr-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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antibodies, Monoclonal / immunology
  • Base Sequence
  • Chlorocebus aethiops / metabolism*
  • Cloning, Molecular
  • DNA, Complementary / genetics
  • Enterovirus / metabolism
  • Epitopes / immunology
  • Fibroblasts / metabolism
  • Fibroblasts / virology*
  • Hepatitis A Virus Cellular Receptor 1
  • Hepatovirus / metabolism*
  • Kidney
  • L Cells
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / isolation & purification*
  • Membrane Glycoproteins / metabolism
  • Mice
  • Mice, Inbred BALB C
  • Molecular Sequence Data
  • Multigene Family
  • Receptors, Virus / genetics
  • Receptors, Virus / immunology
  • Receptors, Virus / isolation & purification*
  • Receptors, Virus / metabolism
  • Sequence Homology, Amino Acid
  • Transfection

Substances

  • Antibodies, Monoclonal
  • DNA, Complementary
  • Epitopes
  • HAVCR1 protein, human
  • Hepatitis A Virus Cellular Receptor 1
  • Membrane Glycoproteins
  • Receptors, Virus

Associated data

  • GENBANK/X98252