FURTHER CHARACTERIZATION OF 2 TYPES OF PRECORE VARIANT HEPATITIS-B VIRUS ISOLATES FROM HONG-KONG

Two precore variants of hepatitis B virus occur in chronic carriers in the Chinese community in Hong Kong. One variant has a serine at amino acid(aa) 15, and the other has a stop codon at aa 28, which inhibits production of hepatitis B e (HBe) antigen (Ag). The serine 15 strain i s shown here to produce antigenically normal amounts of HBeAg. These v ariants are mutually exclusive, probably due to sequence requirements for encapsidation, and are separate lineages. Sequential core sequence s from patients with either variant revealed more aa substitutions in those who have the codon 28 change (P = .02), particularly T helper an d B cell epitopes, implying different selection pressures. Most substi tutions occurred around the time of selection of the stop codon, imply ing that complete loss of HBeAg, an immunomodulatory protein, is neces sary for immune pressure on core epitopes. Serine 15 strains select sm all numbers of substitutions throughout the anti-HBe phase, probably b ecause of persistent immunomodulation.