Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance
Korniy, Natalia ; Goyal, Akanksha ; Hoffmann, Markus ; Samatova, Ekaterina ; Peske, Frank ; Pöhlmann, Stefan ; Rodnina, Marina V.
Citable Link (URL):http://resolver.sub.uni-goettingen.de/purl?gs-1/16451
A hallmark of translation in human immunodeficiency virus type 1 (HIV-1) is a -1 programmed ribosome frameshifting event that produces the Gag-Pol fusion polyprotein. The constant Gag to Gag-Pol ratio is essential for the virion structure and infectivity. Here we show that the frameshifting efficiency is modulated by Leu-tRNALeu that reads the UUA codon at the mRNA slippery site. This tRNALeu isoacceptor is particularly rare in human cell lines derived from T-lymphocytes, the cells that are targeted by HIV-1. When UUA decoding is delayed, the frameshifting follows an alternative route, which maintains the Gag to Gag-Pol ratio constant. A second potential slippery site downstream of the first one is normally inefficient but can also support -1-frameshifting when altered by a compensatory resistance mutation in response to current antiviral drug therapy. Together these different regimes allow the virus to maintain a constant -1-frameshifting efficiency to ensure successful virus propagation.