EMERGENCE OF AN S-GENE MUTANT DURING THYMOSIN ALPHA(1) THERAPY IN A PATIENT WITH CHRONIC HEPATITIS-B

The presence of a hepatitis B virus S gene mutant was investigated in a patient being treated with thymosin alpha(1). He was seropositive fo r hepatitis B e antigen throughout therapy but was intermittently sero negative for hepatitis B surface antigen (HBsAg) by an RIA, Sequence a nalysis revealed an S gene mutant in HBsAg-seronegative serum with two consecutive amino acid substitutions: threonine(115)-to-isoleucine an d threonine(116)-to-asparagine, whereas no amino acid substitution or deletion was found in the pre-S region. A site-directed mutagenesis ex periment confirmed that these mutations were responsible for the failu re to detect HBsAg, In summary, an S gene mutant was identified in an HBsAg-seronegative patient. The mutations were located outside the put ative ''a'' determinant. The emergence of an S gene mutant during thym osin alpha(1) treatment suggests that enhanced host immunity against H BsAg may play a role in its antiviral activity.