Hepatitis A virus (HAV), a picornavirus, is the causative agent of acute hepatitis. Like other picornaviruses, HAV is assumed to enter the cell by first binding to a specific cellular receptor. Interaction of HAV with its cellular receptor could be responsible for many characteristics of HAV such as growth restriction in primate cells and hepatovirulence. Therefore, study of the interaction of HAV with its cellular receptor will help to understand the mechanisms involved in the pathogenicity of this virus and specific receptor antagonists could be useful therapeutic agents. We have recently identified HAVcr-1, a surface glycoprotein on African green monkey kidney (AGMK) cells, as a receptor for hepatitis A virus (EMBO J. 15:4282-4269, 1996). Molecular cloning and sequence analysis of HAVcr-1 cDNA from several monkey cell lines showed that this receptor is polymorphic. Monoclonal antibody 190/4, which protected AGMK cells against HAV infection failed to react with HAVcr-1 cloned from BS-C-1 and CV-1 cells. HAVcr-1 human homolog genes were mapped to chromosomes 1, 5, and 19 and shown to be expressed in certain human tissues including liver. It is not known if the HAvcr-1 homologs also function as HAV receptors. Transgenic mice expressing HAVcr-1 under the control of the RSV LTR promoter were developed. Three transgenic lines carrying different copies of the HAVcr-1 cDNA were obtained. Transgenic animals were infected with HAV and we are analyzing whether HAV can replicate and cause disease in these animals. This study may result in a small animal model for pathogenesis of HAV.
