Laboratory of Molecular and Cellular Virology, Virology Program, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
HIV/AIDS Workgroup, Faculty of Medicine, Universidad de Chile, Santiago, Chile.
RNA Biol. 2021 May;18(5):745-758. doi: 10.1080/15476286.2020.1832375. Epub 2020 Oct 25.
Translation initiation of the human immunodeficiency virus type-1 (HIV-1) full-length RNA has been shown to occur through cap-dependent and IRES-driven mechanisms. Previous studies suggested that the nuclear cap-binding complex (CBC) rather than eIF4E drives cap-dependent translation of the full-length RNA and we have recently reported that the CBC subunit CBP80 supports the function of the viral protein Rev during nuclear export and translation of this viral transcript. Ribosome recruitment during CBC-dependent translation of cellular mRNAs relies on the activity CBP80/20 translation initiation factor (CTIF), which bridges CBP80 and the 40S ribosomal subunit through interactions with eIF3g. Here, we report that CTIF inhibits HIV-1 and HIV-2 Gag synthesis from the full-length RNA. Our results indicate that CTIF associates with HIV-1 Rev through its N-terminal domain and is recruited onto the full-length RNA ribonucleoprotein complex in order to interfere with Gag synthesis. We also demonstrate that CTIF induces the cytoplasmic accumulation of Rev impeding the association of the viral protein with CBP80. We finally show that Rev interferes with the association of CTIF with CBP80 indicating that CTIF and Rev compete for the CBC subunit.
人类免疫缺陷病毒 1 型（HIV-1）全长 RNA 的翻译起始已被证明通过帽依赖性和 IRES 驱动机制发生。先前的研究表明，核帽结合复合物（CBC）而不是 eIF4E 驱动全长 RNA 的帽依赖性翻译，我们最近报道 CBC 亚基 CBP80 支持病毒蛋白 Rev 在核输出和该病毒转录物翻译期间的功能。在 CBC 依赖性细胞 mRNA 翻译过程中核糖体募集依赖于 CBP80/20 翻译起始因子（CTIF）的活性，该因子通过与 eIF3g 的相互作用将 CBP80 和 40S 核糖体亚基桥接。在这里，我们报告 CTIF 通过其 N 端结构域抑制全长 RNA 上的 HIV-1 和 HIV-2 Gag 合成，并招募到全长 RNA 核糖核蛋白复合物以干扰 Gag 合成。我们还证明 CTIF 诱导 Rev 的细胞质积累，阻碍病毒蛋白与 CBP80 的结合。我们最后表明 Rev 干扰 CTIF 与 CBP80 的结合，表明 CTIF 和 Rev 竞争 CBC 亚基。
