2 Mechanisms of Translational Suppression Used in the Biosynthesis of Reverse Transcriptase

Abstract

INTRODUCTION
In all retrovirases, reverse transcriptase is encoded downstream from the gag gene in a large coding region. This coding region is translated by mechanisms discussed below to yield a Gag-Pol fusion protein; this polyprotein is subsequently cleaved by the viral protease to generate the mature reverse transcriptase present in the infectious virion.

The mechanisms of expression of the pol-coding region are now partially understood, and they are the principal subject of this chapter. These mechanisms are of interest not only because they are involved in viral replication, but also because they reveal unexpected capabilities of the translational apparatus of the host cell. In turn, an understanding of these mechanisms may help shed light on cellular regulatory processes and may also provide new approaches for combating virus infection.

In the most general terms, these mechanisms can be outlined as follows. The genomic RNA of the virus is the messenger RNA for the internal structural proteins of the virus (termed the Gag proteins) and for the viral enzymes, including reverse transcriptase. As indicated in Figure 1, the gag-coding sequences are found at the 5′ end of this mRNA. The coding region for the enzymes (generally referred to as the pol gene) is 3′ of the gag gene, with no independent initiation codon. Most of the ribosomes engaged in Gag protein synthesis terminate peptide chain elongation in response to this termination codon (as would be expected), resulting in the synthesis of the Gag polyprotein. However, a minority of these ribosomes engage in...