REGULATION OF HIV RNA PROCESSING AND TRANSPORT

描述：HIV-RNA转运/剪接控制的机制涉及 反式作用病毒蛋白（Rev）结合顺式作用 病毒RNA中的RRE（RRE）。 相比之下，梅森-辉瑞公司的基因组 猴病毒（MPMV）是一种简单的逆转录病毒，含有顺式作用元件 被称为组成型转运元件（CTE）， 与细胞因子作用以实现含内含子RNA的转运。 的 研究者建议进一步研究Rev/RRE和CTE调节， 核质RNA输出。 这项建议的具体目标是：1） 分离和功能性鉴定与细胞相互作用的蛋白质 2）为了鉴定和表征新的 细胞和病毒CTE以及潜在的细胞RRE，3）为了进一步分析 用于Rev/RRE和CTE介导的RNA输出的途径，以及4） 进一步表征HIV-1的变体，其显示出对RevM 10的抗性， 分析不同反式显性基因对HIV复制的抑制作用 使用Rev依赖性和Rev非依赖性病毒的阴性Rev蛋白。 的 提出的实验旨在阐明RNA输出途径如何 Rev/RRE使用的与CTE使用的相关。 它们也可能导致 增加了对细胞RNA输出途径的了解。 一个 了解逆转录病毒RNA的输出与细胞内 RNA可能使我们能够设计具有选择性作用的新型抑制剂。

DESCRIPTION: The mechanism of HIV-RNA transport/splicing control involves the action of a trans-acting viral protein (Rev) that binds to a cis-acting element in the viral RNA (the RRE). In contrast, the genome of Mason-Pfizer Monkey Virus (MPMV), a simpler retrovirus, contains a cis-acting element known as the constitutive transport element (CTE) that interacts directly with cellular factors to effectuate transport of intron-containing RNA. The investigator proposes to further study Rev/RRE and CTE regulation of nucleo-cytoplasmic RNA export. The specific aims of this proposal are: 1) To isolate and functionally characterize cellular proteins that interact specifically with the MPMV CTE, 2) To identify and characterize novel cellular and viral CTEs and potential cellular RRE's, 3) To further analyze the pathways utilized for Rev/RRE and CTE mediated RNA export, and 4) To further characterize variants of HIV-1 that show resistance to RevM10 and to analyze the inhibition of HIV replication by different transdominant negative Rev proteins using Rev-dependent and Rev-independent viruses. The experiments proposed are designed to elucidate how the RNA export pathway utilized by Rev/RRE relates to that used by the CTE. They may also lead to an increased insight into pathways involved in export of cellular RNAs. An understanding of how retroviral RNA export relates to export of cellular RNAs may allow us to design novel inhibitors with selective effects.