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29 Replication of the Hepatitis Virus Genome

Christoph Seeger, William S. Mason


Five strains of hepadnavirus have been identified. The prototype is human hepatitis B virus (HBV), first described as a primary cause of post-transfusion hepatitis (Blumberg et al. 1967). Very similar viruses have been isolated from woodchucks (Summers et al. 1978) and Beechey ground squirrels (Marion et al. 1980), and more distantly related viruses have been described in domestic ducks (Mason et al. 1980) and gray herons (Sprengel et al. 1988). With a genome size of 3 kbp, the hepadnaviruses are among the smallest of animal viruses. Despite this, these viruses are able to reproduce to high levels and to maintain a chronic, productive infection, often in the face of a vigorous immune response. Infection and replication take place primarily in the hepatocyte, the major parenchymal cell of the liver; are noncytopathic; and may persist for the lifetime of the host. All of these viruses are blood-borne and are poorly transmittable except by contact with the blood or blood-contaminated products from an infected individual. Nonetheless, infection can efficiently spread through a population, as revealed by the fact that more than 200 million people are currently infected by human hepatitis B virus.

Hepadnaviral DNA replication is of considerable interest because it occurs via reverse transcription of a viral RNA (Summers and Mason 1982), the pregenome, but in virtually all other 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, and...

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