Transcriptome resources for comparative primate models of lentivirus infection

描述（由申请人提供）：该 R24 申请的目标是为基线以及 HIV 和 SIV 感染期间的几种免疫细胞类型生成完整转录组参考数据库，重点是致病性和非致病性感染的比较模型。我们预计这些数据库将成为艾滋病发病机制、预防和治疗研究的新颖且有价值的资源。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方面以及 Silvestri 博士在艾滋病研究方面的互补专业知识。 在目标 1 中，我们将为四种灵长类动物（人类、恒河猴、RM、黑白眉猴、SM 和非洲绿猴，AGM）中的几个关键免疫细胞亚群（“免疫组”）生成基线参考转录组，这些物种代表了艾滋病研究中最常用的模型。我们将对每个物种的细胞类型进行分类，并分离出 RNA，并由 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组，但在致病性 RM 和非致病性 AGM 模型中发生急性 SIV 感染。在目标 3 中，我们将为相同的免疫细胞生成参考转录组，但在人类、RM、SM 和 AGM 的慢性 HIV 和 SIV 感染的背景下。 我们相信这些资源的潜在影响是巨大的。资源应用包括：(i) 改进已测序物种的基因模型，并协助新物种的基因组组装/注释（即 SM 和 AGM）； (ii) 开发用于艾滋病相关系统生物学研究的工具（例如物种特异性基因探针或微阵列）； (iii) 研究急性和慢性感染期间慢病毒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、转化和临床研究。

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.