The human immunodeficiency virus (HIV) Gag and Gag-Pol polyproteins contain the viral structural proteins and enzymes. Both Gag and Gag-Pol are translated from the same viral RNA but translation of Gag-Pol depends on ribosomal frameshifting.  A constant Gag to Gag-Pol ratio is required for HIV infectivity. However, the determinants controlling frameshifting have been unclear.

The present study conducted by the laboratory of Prof. Marina Rodnina, Max Planck Institute for Biophysical Chemistry, Göttingen, in collaboration with the Infection Biology Unit shows that a tRNA, which binds to the slippery site - the site where the frameshift occurs - can determine frameshifting efficiency. Expression of this tRNA is low in important HIV target cells and under those circumstances the virus can use an alternative frameshifting route. Finally, a second slippery side is present in the viral RNA and can be used for efficient frameshifting once the virus acquires mutations that confer resistance to antiviral therapy. Collectively, the study shows that HIV has several options to ensure the production of constant Gag to Gag-Pol ratios. The results have been published in the renowned journal Nucleic Acid Research.