INFECTIVITY AND PATHOGENICITY IN CHIMPANZEES OF A SURFACE GENE MUTANTOF HEPATITIS-B VIRUS THAT EMERGED IN A VACCINATED INFANT

Hepatitis B virus (HBV) variants with amino acid mutations in the a ep itope of the major surface protein have been identified, and questions have been raised regarding their biologic properties. Dilutions of se rum that contained the first such described HBV mutant, with an Arg-fo r-Gly substitution at codon 145 of the S gene, were inoculated into 6 seronegative chimpanzees. Five of the animals developed serologic and/ or biochemical evidence of hepatitis B. A polymerase chain reaction-ba sed assay that discriminated between the wild type and mutant viral ge nomes revealed that a pure population of the mutant genome was present in the 10(-6) and 10(-7) dilutions of the index serum, resulting in i nfection of the chimpanzees receiving these dilutions only with the mu tant virus. A clone of the mutant virus replicated normally following transfection in vitro. Thus, this HBV surface gene mutant is viable, i nfectious, and pathogenic in chimpanzees.