Lifeboat Foundation

Genome and Structure:

HIV’s genome is a 9.7 kb linear positive-sense ssRNA.¹ There is a m⁷G-cap (specifically the standard eukaryotic m⁷GpppG as added by the host’s enzymes) at the 5’ end of the genome and a poly-A tail at the 3’ end of the genome.² The genome also has a 5’-LTR and 3’-LTR (long terminal repeats) that aid its integration into the host genome after reverse transcription, that facilitate HIV genetic regulation, and that play a variety of other important functional roles. In particular, it should be noted that the integrated 5’UTR contains the HIV promoter called U3.^3,4

HIV’s genome translates three polyproteins (as well as several accessory proteins). The Gag polyprotein contains the HIV structural proteins. The Gag-Pol polyprotein contains (within its Pol component) the enzymes viral protease, reverse transcriptase, and integrase. The Gag-Pol polyprotein is produced via a −1 ribosomal frameshift at the end of Gag translation. Because of the lower efficiency of this frameshift, Gag-Pol is synthesized 20-fold less frequently than Gag.⁵ The frameshift’s mechanism depends upon a slippery heptanucleotide sequence UUUUUUA and a downstream RNA secondary structure called the frameshift stimulatory signal (FSS).⁶ This FSS controls the efficiency of the frameshift process.