Biosynthesis of the reverse transcriptase of hepatitis B viruses involves de novo translational initiation not ribosomal frameshifting

Abstract

Retroviruses and many other types of genetic elements replicate by reverse transcription of RNA (for reviews, see refs 1 and 2). Although structurally and biologically very diverse, such elements carry conserved polymerase genes (pol) that encode proteins required for reverse transcription³. In most cases, the pol gene is preceded by an overlapping gene encoding one or more nucleocapsid proteins⁴, in a different reading frame. Because both coding regions are represented in a single mRNA, the question arises of how the reverse transcriptase in the alternative reading frame is expressed. In retroviruses and retrotransposons it is expressed as a nucleocapsid-polymerase fusion protein by ribosomal frameshift-ing during translation of the overlapping region^5–8. We have examined the mechanism of polymerase biosynthesis in another family of animal viruses that use reverse transcription, the hepatitis B viruses. Genetic and biochemical studies reveal that these viruses do not use ribosomal frameshifting to generate this enzyme, but instead direct translation initiation at an internal initiation (AUG) codon in the polymerase gene.