Emergence of an S gene mutant during thymosin α1 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 for hepatitis B e antigen throughout therapy but was intermittently seronegative for hepatitis B surface antigen (HBsAg) by an RIA, Sequence analysis revealed an S gene mutant in HBsAg-seronegative serum with two consecutive amino acid substitutions: threonine(115)-to-isoleucine and threonine(116)-to-asparagine, whereas no amino acid substitution or deletion was found in the pre-S region. A site-directed mutagenesis experiment confirmed that these mutations were responsible for the failure to detect HBsAg, In summary, an S gene mutant was identified in an HBsAg-seronegative patient. The mutations were located outside the putative "a" determinant. The emergence of an S gene mutant during thymosin alpha(1) treatment suggests that enhanced host immunity against HBsAg may play a role in its antiviral activity.