REGULATION OF HIV RNA PROCESSING AND TRANSPORT

描述：HIV-RNA转运/剪接控制的机制包括 反式作用病毒蛋白(REV)结合顺式作用蛋白的作用 病毒核糖核酸(RRE)中的元件。相比之下，梅森-辉瑞的基因组 猴病毒(MPMV)是一种较简单的逆转录病毒，含有顺式作用元件 称为直接相互作用的构成传输元件(CTE) 与细胞因子一起实现内含子RNA的运输。这个 调查员建议进一步研究REV/RRE和CTE法规 核质RNA输出。这项建议的具体目的是：1) 分离和鉴定相互作用的细胞蛋白 特别是利用MPMV CTE，2)识别和表征小说 细胞和病毒CTE和潜在的细胞RRE，3)进一步分析 REV/RRE和CTE介导的RNA输出的途径，以及4)到 进一步鉴定表现出对RevM10和TO抗药性的HIV-1变种 分析不同易位基因对HIV复制的抑制作用 使用REV依赖和REV非依赖病毒的阴性REV蛋白。这个 提出的实验旨在阐明RNA输出途径是如何 REV/RRE使用的数据与CTE使用的数据有关。它们还可能导致 对参与细胞RNA输出的途径有了更深入的了解。一个 了解逆转录病毒RNA输出与细胞输出之间的关系 RNA可能会让我们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.