THE ROLE OF INTRACELLULAR TRAFFIC IN HIV INFECTION

跨核膜的运输是一个必要的组成部分， 人类免疫缺陷病毒（HIV）的生命周期。 一旦进入 在细胞质中，HIV RNA被逆转录成双链DNA， 然后必须进入细胞核。 越来越多的证据表明， HIV的病毒基质蛋白作为该运输事件的介体。 正在努力确定基质蛋白如何参与 在DNA-RNA-蛋白质复合物的核运输中。 此外，其他 逆转录病毒调节蛋白也进入细胞核， 转录物被输出到细胞质中。 病毒蛋白， 和tat，已被确定为转录的关键调节因子 以及HIV包膜mRNA从细胞核中的运输。 这些蛋白质 包含靶向所述细胞所必需且足够的序列， 核仁 使用透化细胞的体外系统已经被公开。 开发来观察携带这种蛋白质的核仁靶向， 瞄准信号 这种核仁定位是通过还原 将温度降至4 ℃或省略ATP。 这表明 向核仁的运输是一个主动过程。 近日有 证明了细胞GTP水平的降低， IMP-脱氢酶的抑制剂减少了 其他核仁蛋白质。 然而，这些抑制剂，包括 利巴韦林和麦考酚酸，不影响核仁积累 的模型蛋白质在透化细胞。 此外，100倍 在体外试验中，GTP水平的降低不影响核仁 模型蛋白的积累。 我们的研究表明， 具有快速周转率的蛋白质可能是观察到的 IMP脱氢酶抑制剂对核仁靶向的影响。 换句 研究中，核孔的结构已被检查。 核 已从非洲爪蟾卵提取物与外源性 DNA. 重构的细胞核在许多方面模仿间期核， 进行活跃的核运输， 类似于核仁。 核孔需要糖蛋白成分 以保证其形态和功能。

Transport across the nuclear membrane is a necessary component of the life cycle of the human immunodeficiency virus (HIV). Once in the cytoplasm, HIV RNA is reverse-transcribed into double-stranded DNA which then must enter the nucleus. A growing amount of evidence points to the viral matrix protein of HIV as a mediator of this transport event. Efforts are underway to determine how the matrix protein may be involved in nuclear transport of the DNA-RNA-protein complex. In addition, other retroviral regulatory proteins also enter the nucleus, and viral transcripts are exported out to the cytoplasm. The viral proteins, rev and tat, have been identified as a key regulators of the transcription and transport of HIV envelope mRNA out of the nucleus. These proteins contain sequences that are necessary and sufficient for targeting to the nucleolus. An in Vitro system using permeabilized cells has been developed to look at the nucleolar targeting of proteins bearing such targeting signals. This nucleolar localization is blocked by reducing the temperature to 4 degrees C or by omitting ATP. This suggests that transport to the nucleolus is an active process. Recently, it has been demonstrated that a reduction in cellular GTP levels induced by inhibitors of IMP-dehydrogenase reduce the nucleolar accumulation of other nucleolar proteins. However, these inhibitors, which include ribavirin and mycophenolic acid, did not affect nucleolar accumulation of the model protein in permeabilized cells. Moreover, an 100-fold reduction of GTP levels in the in vitro assay did not affect nucleolar accumulation of the model protein. Our studies suggest that the loss of a protein with a rapid turnover rate may be responsible for the observed effect of IMP dehydrogenase inhibitors on nucleolar targeting. In other studies, the structure of the nuclear pore has been examined. Nuclei have been reconstituted from Xenopus laevis egg extracts with exogenous DNA. The reconstituted nuclei mimic interphase nuclei in many ways and carry out active nuclear transport, and also contain structures resembling nucleoli. The nuclear pore requires glycoprotein components for proper morphology and function.