HIV-1 基因组中 TAR 发夹结构的打开导致异常的 RNA 二聚化和包装。

Opening of the TAR hairpin in the HIV-1 genome causes aberrant RNA dimerization and packaging.

机构信息

Laboratory of Experimental Virology, Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands.

出版信息

Retrovirology. 2012 Jul 24;9:59. doi: 10.1186/1742-4690-9-59.

BACKGROUND

The TAR hairpin is present at both the 5' and 3' end of the HIV-1 RNA genome. The 5' element binds the viral Tat protein and is essential for Tat-mediated activation of transcription. We recently observed that complete TAR deletion is allowed in the context of an HIV-1 variant that does not depend on this Tat-TAR axis for transcription. Mutations that open the 5' stem-loop structure did however affect the leader RNA conformation and resulted in a severe replication defect. In this study, we set out to analyze which step of the HIV-1 replication cycle is affected by this conformational change of the leader RNA.

RESULTS

We demonstrate that opening the 5' TAR structure through a deletion in either side of the stem region caused aberrant dimerization and reduced packaging of the unspliced viral RNA genome. In contrast, truncation of the TAR hairpin through deletions in both sides of the stem did not affect RNA dimer formation and packaging.

CONCLUSIONS

These results demonstrate that, although the TAR hairpin is not essential for RNA dimerization and packaging, mutations in TAR can significantly affect these processes through misfolding of the relevant RNA signals.

背景

TAR 发夹存在于 HIV-1 RNA 基因组的 5' 和 3' 末端。5' 元件结合病毒 Tat 蛋白，对于 Tat 介导的转录激活至关重要。我们最近观察到，在不依赖 Tat-TAR 轴进行转录的 HIV-1 变体中，完全缺失 TAR 是允许的。然而，打开 5' 茎环结构的突变会影响前导 RNA 构象，并导致严重的复制缺陷。在这项研究中，我们着手分析前导 RNA 构象变化影响 HIV-1 复制周期的哪个步骤。