NATURALLY-OCCURRING ESCAPE MUTANTS OF HEPATITIS-B VIRUS WITH VARIOUS MUTATIONS IN THE S-GENE IN CARRIERS SEROPOSITIVE FOR ANTIBODY TO HEPATITIS-B SURFACE-ANTIGEN

Hepatitis B virus (HBV) DNA was extracted from sera of six carriers wi th hepatitis B e antigen as well as antibody to hepatitis B surface an tigen and sequenced within the pre-S regions and the S gene. HBV DNA c lones from five of these carriers had point mutations in the S gene, r esulting in conversion from Ile-126 or Thr-126 of the wild-type virus to Ser-126 or Asn-126 in three carriers and conversion from Gly-145 to Arg-145 in three of them; clones with Asn-126 or Arg-145 were found i n one carrier. All 12 clones from the other carrier had an insertion o f 24 bp encoding an additional eight amino acids between Thr-123 and C ys-124. In addition, all or at least some of the HBV DNA clones from t hese carriers had in-phase deletions in the 5' terminus of the pre-S2 region. These results indicate that HBV escape mutants with mutations in the S gene affecting the expression of group-specific determinants would survive in some carriers after they seroconvert to antibody agai nst surface antigen. Carriers with HBV escape mutants may transmit HBV either by donation of blood units without detectable surface antigen or through community-acquired infection, which would hardly be prevent ed by current hepatitis B immuneglobulin or vaccines.