Replication of hepatitis B virus in a hepatocellular carcinoma

Hepatitis B virus transcripts and DNA from paired samples of neoplastic and nonneoplastic liver tissue of HBsAg seropositive patients were analyzed. The data obtained support the view that transcription of integrated DNA is frequent, both in neoplastic as well as in nonneoplastic liver tissue. In the case of one patient, integrated and free forms of hepatitis B virus DNA were detected in the tumor. Complete cycles of viral replication in this tumor were suggested by the following markers: (i) DNA and RNA intermediates expected to occur during replication of the viral genome, (ii) HBcAg and HBsAg, (iii) core and Dane particles. Viral DNA cloned from tumor tissue was proven to be replication competent in a transient replication assay. Five independent clones of viral DNA were established and found to be closely related at the nucleotide level. A preX open reading frame and a stop codon within preC were common features. In tissue surrounding the tumor, a nonreplicative state of virus infection prevailed, characterized by free viral DNA exclusively of the covalently closed, circular form. The replication of the viral DNA appeared to be blocked at the level of transcription.