THE ROLE OF INTRACELLULAR TRAFFIC IN HIV INFECTION

在生命周期中，核膜运输是必要的

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.