PRODUCTION OF HEPATITIS-B VIRUS COVALENTLY CLOSED CIRCULAR DNA IN TRANSFECTED CELLS IS INDEPENDENT OF SURFACE-ANTIGEN SYNTHESIS

Covalently closed circular DNA (cccDNA) is the first hepatitis B virus (HBV) DNA replicative intermediate formed from the genomic DNA and se rves as the template for synthesis of viral mRNA and pregenomic RNA. I t also appears to be produced by intracellular recycling of relaxed ci rcular DNA intermediates. Here, we report that none of the forms of HB V surface antigen affect this intracellular recycling of HBV DNA. Elim ination of the initiation codons for the large and middle surface prot eins did not affect the detection of surface antigen in culture supern atants. In contrast, detection of surface antigen was eliminated by th e removal of, or the introduction of two stop codons downstream of, th e initiation codon of the small (major) surface antigen. None of the m utations affected the production, in transfected HepG2 cells, of HBV D NA replicative intermediates, including cccDNA.