Fassati Ariberto, Görlich Dirk, Harrison Ian, Zaytseva Lyubov, Mingot José-Manuel
The Wohl Virion Centre, Windeyer Institute, University College London Medical School, 46 Cleveland Street, London W1T 4JF, UK.
EMBO J. 2003 Jul 15;22(14):3675-85. doi: 10.1093/emboj/cdg357.
Human immunodeficiency virus type 1 (HIV-1), like other lentiviruses, can infect non-dividing cells. This property depends on the active nuclear import of its intracellular reverse transcription complex (RTC). We have studied nuclear import of purified HIV-1 RTCs in primary macrophages and found that importin 7, an import receptor for ribosomal proteins and histone H1, is involved in the process. Nuclear import of RTCs requires, in addition, energy and the components of the Ran system. Depletion of importin 7 from cultured cells by small interfering RNA inhibits HIV-1 infection. These results provide a new insight into the molecular mechanism for HIV-1 nuclear import and reveal potential targets for therapeutic intervention.
1型人类免疫缺陷病毒(HIV-1)与其他慢病毒一样,能够感染非分裂细胞。这一特性取决于其细胞内逆转录复合物(RTC)的主动核输入。我们研究了纯化的HIV-1 RTCs在原代巨噬细胞中的核输入,发现核糖体蛋白和组蛋白H1的输入受体importin 7参与了这一过程。此外,RTCs的核输入需要能量和Ran系统的组分。通过小分子干扰RNA从培养细胞中耗尽importin 7可抑制HIV-1感染。这些结果为HIV-1核输入的分子机制提供了新的见解,并揭示了治疗干预的潜在靶点。