This study reports the molecular cloning of the hepatitis A virus (HAV) receptor from S.la/Ve-1 cells, a simian hybrid cell line highly susceptible to HAV infection. Researchers generated a monoclonal antibody (MAb 2H4) capable of blocking HAV adsorption and used it to screen a cDNA expression library. They identified a 2.1 kb cDNA clone encoding a 460 amino acid glycoprotein containing characteristic structural features including a signal peptide, transmembrane domain, four N-linked glycosylation sites, an immunoglobulin domain, and mucin-like protein regions. To confirm functional receptor activity, the cDNA was expressed in HAV-refractory HeLa cells using a vaccinia virus vector, where it successfully induced HAV attachment that was specifically blocked by MAb 2H4. Immunoprecipitation studies revealed the native protein migrates at 95-120 kDa, indicating extensive post-translational glycosylation. The receptor was detected in HAV-susceptible cell lines but not in refractory lines. These findings identify a functional HAV receptor and provide molecular tools for understanding HAV pathogenesis and infection mechanisms.

Key findings

• A 2.1 kb cDNA encoding a 460 amino acid glycoprotein was cloned from HAV-susceptible S.la/Ve-1 cells and identified as the hepatitis A virus receptor
• The receptor protein contains structural domains typical of cell surface receptors: signal peptide, transmembrane domain, immunoglobulin domain, and mucin-like regions with threonine repeats
• Expression of the cloned cDNA in HAV-refractory HeLa cells conferred specific HAV-binding capacity that was blocked by monoclonal antibody 2H4
• The native receptor protein undergoes extensive glycosylation, migrating at 95-120 kDa despite a predicted molecular weight of 50 kDa from the open reading frame