Transcriptome resources for comparative primate models of lentivirus infection

描述(由申请人提供)：本R24申请的目标是在基线和艾滋病毒和SIV感染期间为几种免疫细胞类型生成完整的转录组参考数据库，重点是病原性和非病原性感染的比较模式。我们预见，这些数据库将成为艾滋病发病机制、预防和治疗研究的新的和有价值的资源。该项目是与下一代测序相关的革命性进步的产物，并利用了Katze博士在系统生物学和生物信息学以及Silvestri博士在艾滋病研究方面的互补专业知识。 在目标1中，我们将为代表艾滋病研究最常用模型的四个灵长类物种(人、恒河猴、RMS、乌贼、SMS和非洲绿猴，AGM)的几个关键免疫细胞亚群(“免疫组”)生成基准参考转录本。我们将对每个物种的细胞类型进行分类，并分离出RNA，然后由Katze实验室进行全面测序。在目标2中，我们将为相同的免疫细胞生成参考转录本，但在致病性RM和非致病性AGM模型中急性SIV感染的背景下。在目标3中，我们将为相同的免疫细胞生成参考转录本，但在人类、RMS、SMS和AGM的慢性HIV和SIV感染的背景下。 我们认为，这些资源的潜在影响是巨大的。资源应用包括：(1)改进已测序物种的基因模型，协助新物种的基因组组装/注释(即短信息系统和动植物模型)；(2)为艾滋病相关系统生物学研究开发工具(如特定物种的基因探针或微阵列)；(3)研究慢病毒在急性和慢性感染期间与免疫系统之间的相互作用。获得的参考转录组信息将用于产生新的假设，设计新的实验，并推进艾滋病毒预防和治疗领域的基础、翻译和临床研究。

DESCRIPTION (provided by applicant): The goal of this R24 application is to generate whole transcriptome reference databases for several immune cell types at baseline and during HIV and SIV infection, with emphasis on the comparative models of pathogenic and non-pathogenic infections. We envision that these databases will serve as novel and valuable resources for studies of AIDS pathogenesis, prevention, and therapeutics. The project is an outgrowth of the revolutionary advances associated with next-generation sequencing, and leverages the complementary expertise of Dr. Katze in systems biology and bioinformatics and of Dr. Silvestri in AIDS research. In Aim 1, we will generate baseline reference transcriptomes for several key immune cell subsets ("immunome") in four primate species (humans, rhesus macaques, RMs, sooty mangabeys, SMs, and African green monkeys, AGMs) that represent the most used models for AIDS research. We will sort cell types from each species, and we will isolate RNA that will be comprehensively sequenced by.the Katze lab. In Aim 2, we will generate reference transcriptomes for the same immune cells but in the context of acute SIV infection in the pathogenic RM and the non-pathogenic AGM models. In Aim 3, we will generate reference transcriptomes for the same immune cells but in the context of chronic HIV and SIV infection in humans, RMs, SMs, and AGMs. We believe that the potential impact of these resources is substantial. Resource applications include: (i) improvements to gene models for already sequenced species and assistance for genome assembly/annotation for new species (i.e., SMs and AGMs); (ii) development of tools (e.g., species-specific gene probes or microarrays) for AIDS-related systems biology research; (iii) investigation ofthe interaction between lentiviruses and the immune system during acute arid chronic infection. The obtained reference transcriptome information will be used to generate new hypotheses, design new experiments, and advance basic, translational, and clinical research in the fields of HIV prevention and therapy.