Hepatitis B virus reverse transcriptase and its many roles in hepadnaviral genomic replication.

Abstract

The replication of hepatitis B virus DNA proceeds through reverse transcription of a pregenomic RNA intermediate, a reaction that takes place within viral nucleocapsids and is catalyzed by the viral P protein. P protein is involved in all phases of the reaction, serving as (a) a recognition factor for the selective encapsidation of the pregenomic RNA template; (b) the protein primer for the initiation of minus strand DNA synthesis; (c) the reverse transcriptase and DNA polymerase involved in strand elongation; and (d) the RNaseH activity required to remove RNA template prior to plus strand synthesis. P protein is capable of site-specific RNA recognition, specifically binding to a stem-loop structure at the 5' end of pregenomic RNA. This interaction is required for both RNA encapsidation and reverse transcription.