MOLECULAR CHARACTERIZATION OF ENVELOPE ANTIGENIC VARIANTS OF HEPATITIS-B VIRUS FROM SPAIN

In a survey of hepatitis B virus (HBV) subtypes using one set of monoc lonal typing antibodies, 96.6% of the samples were ad or ay and 3.3% ( 31) were untypeable. Using two additional antibody panels, 23 samples were ay and ad. Six samples required a third panel to be typed as ay. One sample was not typeable. These last 7 samples were nonreactive or had low reactivity with some antibodies to the common a determinant. S equencing the HBsAg gene of these 7 samples revealed that amino acid ( aa) 122 was arginine, as expected for the y determinant. However, muta tions giving rise to serine at aa 120, leucine at aa 143, and glutamic acid at aa 144 were found singly or in combination and correlated wit h the monoclonal antibody binding patterns. These results have implica tions for further subtyping surveys, vaccines, immunotherapy, and the design of diagnostic assays, and they give clues to the structure of t he major neutralizing epitope of HBV.