Project 5 - HIV-1 Genome Stability & Editing Mediated by Host

项目5：宿主蛋白介导的HIV-1基因组稳定性和编辑 总结 在HIV-1感染的细胞中，许多宿主蛋白质与病毒RNA相互作用。这些相互作用可能具有积极或 对病毒复制的负面影响。其中一些RNA蛋白质相互作用导致基因组的编辑， 而另一些则调节RNA的命运。CRNA研究人员已经发现并表征了这样几种RNA：宿主 蛋白质相互作用构成了项目5的基础。该项目将包括结构和生物的混合 确定这些重要的宿主蛋白-病毒RNA相互作用的确切性质和作用的方法， HIV-1复制。在目标1中，Bieniasz和Smith将确定一种新的二核苷酸的X-晶体结构， 检测与其靶点结合的RNA去稳定化抗病毒蛋白。这种蛋白质似乎具有主要的选择性 这种压力驱动了HIV-1基因组的偏向性核苷酸组成，并且可能是许多人的基因组。 其他病毒。它的发现对于理解选择性的力量有着深远的影响， 病毒及其宿主的核苷酸组成和非自身RNA的检测。对于目标2，APOBEC 3 CRNA研究人员发现，蛋白质通过与病毒RNA相互作用而被整合到病毒体中 似乎模仿HIV-1 NC的序列偏好。因此，Bieniasz，Smith和合作者将 确定与RNA靶或DNA结合的猪尾猕猴和人APOBEC 3 H的晶体结构 衬底最后，Cullen证明了病毒基因组中特定位点的腺苷甲基化 促进HIV-1复制，在该项目的目标3中，Cullen，Replikin和Telesnitsky将确定 m6 A修饰和m6 A结合蛋白对HIV-1 RNA结构和功能的影响及其在HIV-1感染中的作用 1次重复。

Project 5: HIV-1 genome stability and editing mediated by host proteins Summary In HIV-1 infected cells, many host proteins interact with viral RNA. These interactions can have positive or negative effects on viral replication. Some of these RNA protein interactions lead to editing of the genome, while others regulate RNA fate. CRNA investigators have discovered and characterized such several RNA:host protein interactions that form the basis for Project 5. This project will comprise a mix of structural and biological approaches to determine the precise nature and role of these important host protein-viral RNA interactions in HIV-1 replication. In Aim 1 Bieniasz and Smith will determine the X-crystal structure of a novel dinucleotide- sensing RNA-destabilizing antiviral protein bound to its target. This protein appears to impose a major selective pressure that drives the biased nucleotide composition of the HIV-1 genome, and likely the genomes of many other viruses. Its discovery has far reaching implications for the understanding of the selective forces driving nucleotide composition of viruses and their hosts and the detection of non-self RNA. For Aim 2, APOBEC3 proteins were shown by CRNA investigators to be incorporated into virions through interactions with viral RNA that appear to mimic the sequence preference of HIV-1 NC. Therefore, Bieniasz, Smith and collaborators will determine crystal structures of pigtail macaque and human APOBEC3H bound to an RNA target or a DNA substrate. Finally, Cullen has demonstrated that adenosine methylation at specific sites in the viral genome facilitates HIV-1 replication, and in Aim 3 of this project Cullen, Rouskin and Telesnitsky will determine the effect of m6A modification and m6A binding proteins on HIV-1 RNA structure and function, and their role in HIV- 1 replication.