Department of Physical Biochemistry, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, 37077 Göttingen, Germany.
Infection Biology Unit, German Primate Center, Kellnerweg 4, 37077 Göttingen, Germany.
Nucleic Acids Res. 2019 Jun 4;47(10):5210-5222. doi: 10.1093/nar/gkz202.
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.
人类免疫缺陷病毒 1 型（HIV-1）翻译的一个标志是-1 程序性核糖体移码事件，该事件产生 Gag-Pol 融合多聚蛋白。恒定的 Gag 与 Gag-Pol 比率对于病毒粒子结构和感染力至关重要。在这里，我们表明，通过读取 mRNA 滑动位点上的 UUA 密码子的 Leu-tRNALeu 来调节移码效率。这种 tRNALeu 同工受体在源自 T 淋巴细胞的人类细胞系中特别罕见，而 HIV-1 正是靶向这些细胞。当 UUA 解码延迟时，移码遵循替代途径，从而保持 Gag 与 Gag-Pol 比率恒定。第一个滑动位点下游的第二个潜在滑动位点通常效率较低，但在响应当前抗病毒药物治疗的补偿性耐药突变时，也可以支持-1 移码。这些不同的机制共同允许病毒维持恒定的-1 移码效率，以确保病毒的成功传播。
