Horizontal transmission of a hepatitis B virus surface antigen mutant.

The envelope protein of hepatitis B virus (HBV) is referred to as the HBV surface antigen (HBsAg) (8). The antigenic “a” determinant is located from residue 124 to 147 of HBsAg and is involved in eliciting antibody production. Neutralizing antibodies (anti-HBs) target the “a” determinant and generally lead to the disappearance of HBV (1). The coexistence of HBsAg and anti-HBs has been associated with mutations in the “a” determinant (2, 6). Displaying altered antigenic structures, these HBsAg mutants are capable of escaping detection and vaccination (4, 9). Some are infectious and are associated with liver diseases (3–5, 7). While some may be transmitted vertically (6), no horizontal transmission of these HBsAg mutants has previously been described. We report the horizontal transmission of an HBsAg mutant (Asp144Ala) from an infected infant to his wild-type-HBV carrier Singaporan mother who gave birth to two identical twins in 1984. Despite vaccination at birth, both infants tested positive for HBsAg beginnning at birth. The Asp144Ala mutant was detected in the serum of one twin (infant 1) by direct sequencing analysis. While only wild-type HBV was found in the maternal serum taken at delivery and in cord blood (Fig. 1A, panels 1 and 2, respectively), the Asp144Ala HBsAg mutant was detectable in maternal serum taken 6 years later (Fig. 1A, panel 3). To rule out the possibility that a minor population of the Asp144Ala mutant that was undetectable by sequencing was present in the maternal serum at delivery, a PCR-based nucleotide analysis method was developed. The first PCR amplification resulted in a 420-bp fragment (position 420 to 840 of the HBV genome) in the three maternal samples (Fig. 1B, lanes 1 to 3) that were analyzed by the above-mentioned direct sequencing method (Fig. 1A). The second PCR using a nested primer (59-AGGATGATGGGATGGGAATACAGGTGCA TTTTCC-39), with its 39-end nucleotide immediately adjacent to the nucleotide mutation (GAC Asp to GCC Ala [mutation is underlined]), gave rise to a 200-bp fragment (position 420 to