THE ROLE OF INTRACELLULAR TRAFFIC IN HIV INFECTION

在生命周期中，跨核膜运输是必需的 艾滋病病毒。 一旦进入细胞质，HIV RNA就转化为双链， 必须进入细胞核的DNA。 病毒调节蛋白进入 病毒转录物被输出到细胞质中。 病毒 REV和达特蛋白已被鉴定为细胞凋亡的关键调节因子。 转录和运输HIV包膜mRNA。 这些蛋白质 含有将它们靶向到核仁的序列。 近日更 已经证明，细胞GTP水平的降低诱导的 IMP脱氢酶抑制剂减少了 其他核仁蛋白质。 这些抑制剂，包括利巴韦林或 麦考酚酸，正在测试他们的能力，干扰 HIV达特和REV核仁定位。 我们还发明了一种方法 用于在体外围绕外源添加的DNA产生细胞核。 述的方法 使用非洲爪蟾卵的提取物。 原子核以这种方式聚集 通过多种方式提取模拟间期核， 核运输 这些重新形成的细胞核具有类似于 核仁（称为前核仁）。 这些准备工作应使 REV的作用机制和其他分子的运动参与 艾滋病毒的生命周期将在体外进行检查。 在其他研究中， 核孔的结构进行了检查。 核孔 需要糖蛋白组分以获得适当的形态和功能。

Transport across the nuclear membrane is necessary during the life cycle of HIV. Once in the cytoplasm, HIV RNA is converted to double stranded DNA which must enter the nucleus. Viral regulatory proteins enter the nucleus; viral transcripts are exported into the cytoplasm. The viral REV and TAT proteins have been identified as key regulators of the transcription and transport of HIV envelope MRNA. These proteins contain sequences which target them to the nucleolus. 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. These inhibitors, which include ribavirin or mycophenolic acid, are being tested for their ability to interfere with HIV TAT and REV nucleolar localization. A means has also been devised for generating nuclei in vitro around exogenously added DNA. The method uses extracts from Xenopus laevis eggs. The nuclei assembled in such extracts mimic interphase nuclei in many ways and carry out active nuclear transport. These reinformed nuclei have structures resembling nucleoli (termed pre-nucleoli). These preparations should allow the mechanism of REV action and the movement of other molecules involved in the HIV life cycle to be examined in vitro. In other studies the structure of the nuclear pore has been examined. The nuclear pore requires glycoprotein components for proper morphology and function.