Transmission of hepatitis B virus analyzed by conformation-dependent polymorphisms of single-stranded viral DNA

Hepatitis B virus (HBV) DNA from regions coding for surface and core antigens were amplified and radiolabeled from hepatitis B surface antigen (HBsAg)-positive serum samples by polymerase chain reaction, heat-denatured, and analyzed for conformation-dependent polymorphisms by gel electrophoresis under nondenaturation conditions. Analysis of serum samples representative of diverse and identical HBsAg subtypes showed a wide range of autoradiographic banding patterns, each unique to the specimen. Serial samples of a long-term carrier showed relative stability of banding patterns over time. Epidemiologic analyses using this procedure showed banding patterns of case subjects to be identical to those of persons implicated as the source. This facile and discriminatory approach to the differentiation of viral strains should be useful in the study of HBV transmission.