Properties of the Genome

All members of the Hepadnaviridae family have a partially double-stranded DNA genome of about 3 kb that is held in a circular conformation by a short cohesive overlap between the 5' ends of the two DNA strands (Fig. 1). One strand is always complete in virus particles, whereas the second strand is incomplete, with a 3' end that is heterogeneous in location. The incomplete strand is of plus polarity and the complete strand of negative polarity. When these viruses infect a cell, the plus strand is completed and the fully double-stranded DNA is then converted to a covalently-closed circular (CCC) molecule, which serves as a template for viral RNA synthesis (Fig. 2). The two genera of hepadnaviruses are thought to differ in that orthohepadnaviruses encode four open reading frames (ORFs) whereas the prototypic avihepadnavirus, duck hepatitis B virus, encodes only three, lacking the X ORF. This ORF appears to encode a protein that modulates transcription, possibly by acting on signal transduction pathways. There is now evidence for a fourth ORF in heron hepatitis B virus and in Ross goose virus, capable of coding for a 7-8 kDa protein, in the same genomic location as the C-terminal half of the X ORF of the orthohepadnaviruses. Functional studies on this ORF have not been reported. With one exception, the known products of the different ORFs are each translated from distinct mRNAs, transcribed from one of the four {Orthohepadnavirus) or three (Avihepadnavirus) viral promoters. The major nucleocapsid protein and the product of the polymerase gene appear to be encoded by the same mRNA, the pregenome, which also serves as the template for viral DNA synthesis. It was originally thought that mRNA splicing did not have a role in virus replication; however, it was recently found that the larger (L) of the two envelope proteins of duck hepatitis B virus is translated both from a spliced mRNA as well as from an unspliced mRNA. The spliced mRNA is transcribed from the major nucleocapsid promoter, located about 1200 bp upstream of the start codon for the large envelope protein. The unspliced mRNA is synthesized from a promoter located immediately upstream of the ORF for the large envelope protein (Fig. 1).

All hepadnaviruses replicate their DNA by reverse transcription of a viral RNA, a process which takes

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