Modulation of HIV-1 Gag/Gag-Pol frameshifting by tRNA abundance. Issue 10 (10th April 2019)

• Record Type: Journal Article
• Authors: Korniy, Natalia; Goyal, Akanksha; Hoffmann, Markus; Samatova, Ekaterina; Peske, Frank; Pöhlmann, Stefan; Rodnina, Marina V
• Is Part Of: Nucleic acids research. Volume 47:Issue 10(2019)
• Page Start: 5210
• Page End: 5222
• Publication Date: 2019-04-10
• Subjects: Nucleic acids -- Periodicals; Molecular biology -- Periodicals; 572.805
• DOI: 10.1093/nar/gkz202
• Languages: English
• ISSNs: 0305-1048

Abstract

Abstract: 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-tRNA Leu that reads the UUA codon at the mRNA slippery site. This tRNA Leu 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.