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36 Hepadnavirus

Christoph Seeger, William S. Mason


There are five species of hepadnavirus belonging to two different genera. The prototype is human hepatitis B virus (HBV), an orthohepadnavirus, first described as a primary cause of post-transfusion hepatitis. Species closely related to HBV have been isolated from the woolly monkey, woodchuck, and Beechey ground squirrel, and more distantly related viruses (avihepadnaviruses) have been described in domestic ducks, gray herons, storks, cranes, and geese (for review, see Seeger and Mason 2000).

All hepadnaviruses have a 3-kbp relaxed circular (rc), partially double-stranded DNA genome (Fig. 1), replicate to high levels, and maintain a chronic, productive infection, often in the face of a vigorous immune response. Virus replication occurs primarily in the hepatocyte, the major parenchymal cell of the liver. Infection and virus replication do not lead to hepatocyte death, which results instead from the host immune response. All of these viruses circulate in the bloodstream and are poorly transmittable except by contact with blood or blood-contaminated products from infected individuals. Nonetheless, infection can efficiently spread through a population. Over 350 million people are chronically infected by human HBV and are at high risk of developing cirrhosis and hepatocellular carcinoma.

Hepadnaviral DNA replication occurs via reverse transcription of a viral RNA, the pregenome, but in virtually all details, differs from the reverse transcription pathway evolved by retroviruses. In fact, the hepadnavirus provirus is an episomal, covalently closed circular (CCC) DNA, and not the integrated DNA of the retrovirus. Since most retroviruses are only able to complete provirus integration and subsequent expression...

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