title: Biosynthesis of hepatitis B virus e antigen: directed mutagenesis of the putative aspartyl protease site.
abstract: The C gene products of all mammalian hepadnaviruses contain a region with sequence similarities to the catalytic center of the aspartyl proteases. This region could have the capacity to cleave precore proteins, leading to the synthesis of e antigen. By site-directed mutagenesis on a plasmid containing the hepatitis B virus C gene, we have replaced either the Asp residue of the putative aspartyl protease catalytic center or an Asp residue located 3 amino acids upstream. Transient expression of the mutated hepatitis B virus C gene in human and mouse cells showed that none of these mutations prevented the secretion of an accurately processed HBe antigen. Thus, we demonstrated that the aspartyl protease responsible for e antigen precursor processing is not C gene encoded but is more likely to be a cellular enzyme. From these results, we suggest a model for the mechanism of e antigen synthesis.
authors.affiliation: Laboratoire de Biologie Moléculaire de la Réplication, ER 272-Centre National de la Recherche Scientifique, Villejuif, France.
authors.forename: O
authors.initials: O
authors.lastname: Jean-Jean
authors.forename: S
authors.initials: S
authors.lastname: Salhi
authors.forename: D
authors.initials: D
authors.lastname: Carlier
authors.forename: C
authors.initials: C
authors.lastname: Elie
authors.forename: A M
authors.initials: AM
authors.lastname: De Recondo
authors.forename: J M
authors.initials: JM
authors.lastname: Rossignol
mesh_terms: D000595:Amino Acid Sequence; D016282:Aspartic Acid Endopeptidases; D001483:Base Sequence; D010450:Endopeptidases / Q000235:genetics*; D005814:Genes, Viral; D006513:Hepatitis B e Antigens / Q000235:genetics*; D006515:Hepatitis B virus / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D007256:Information Systems; D008969:Molecular Sequence Data; D009154:Mutation; D015183:Restriction Mapping; D012689:Sequence Homology, Nucleic Acid; D015678:Viral Structural Proteins / Q000235:genetics*
chemical_list: D006513:Hepatitis B e Antigens; D015678:Viral Structural Proteins; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases