15 Reverse Transcription Pathway of the Hepatitis B Viruses

Abstract

All genetic elements that carry out reverse transcription must solve a common set of problems to effect this complex reaction. These include (1) directing the synthesis of the appropriate RNA template and of the reverse transcriptase itself, (2) assembling these components into a replication complex, (3) initiating and elongating first-strand DNA synthesis on the RNA template, (4) degrading the RNA of the resulting DNA-RNA hybrid to allow the first DNA strand to template the synthesis of the second, and (5) priming and completing second-strand DNA synthesis to generate a duplex DNA product. Until recently, these reactions were understood in detail only for retroviruses (and for retrotransposons like yeast Ty elements whose overall mechanism is closely similar). However, recent studies of reverse transcription in hepatitis B viruses (HBVs) have led to an understanding of this reaction that is nearly as detailed as that of cognate events in retroviral replication. Contrary to expectation, these studies have shown that at nearly every step in the reverse transcription pathway, HBVs have solved the aforementioned common problems in remarkably different ways. In this chapter, we review what is currently known about reverse transcription in HBVs, with particular reference to divergences from the retroviral paradigm.

VIRUS STRUCTURE AND REPLICATION: AN OVERVIEW
Human HBV is the prototype member of a distinctive family of viruses called hepadnaviruses (for hepatotropic DNA viruses); related viruses exist among several other species, including woodchucks, ground squirrels, and ducks (Marion 1988). All hepadnaviruses replicate preferentially (but not exclusively) in the liver, where they...