EMERGENCE OF HEPATITIS-B VIRUS S-GENE MUTANT IN A LIVER-TRANSPLANT RECIPIENT

Immunological and genomic analysis of the ''a'' determinant was carrie d out in seven patients with concurrent HBsAg and anti-HBs, four of wh om were immunized against hepatitis B virus at liver transplant, two w ith histologically characterized chronic hepatitis B virus infection, and one HBsAg healthy carrier. The immune reactivity of the HBsAg ''a' ' determinant was evaluated by binding to specific monoclonal antibodi es, and the corresponding genomic sequence was studied by differential hybridization in microtiter plates and nucleotide sequence analysis. A double mutation generating an amino acid change (glycine to lysine) at residue 145, able to impair recognition by monoclonal antibodies, w as observed in the post-transplant serum from one patient. No signific ant alteration of the ''a'' determinant sequence or reactivity was det ected in the other patients. Amino acid residue 145 appears therefore to be critical for the recognition by anti-HBs antibodies. A previousl y undescribed glycine to lysine substitution at this level interferes with the immune reactivity of the ''a'' determinant. (C) 1995 Wiley-Li ss, Inc.