Transcriptome resources for comparative primate models of lentivirus infection

描述（由申请人提供）：该R24应用程序的目标是在基线和HIV和SIV感染期间生成几种免疫细胞类型的全转录组参考数据库，重点是病原性和非病原性感染的比较模型。我们设想，这些数据库将作为艾滋病发病机制，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展的产物，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，我们将为代表艾滋病研究最常用模型的四种灵长类物种（人类、恒河猴、RM、非洲白眉猴、SM和非洲绿色猴、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。我们将对每个物种的细胞类型进行分类，我们将分离出RNA，这些RNA将由Katze实验室进行全面测序。在目标2中，我们将在致病性RM和非致病性AGM模型中的急性SIV感染的背景下为相同的免疫细胞产生参考转录组。在目标3中，我们将为相同的免疫细胞产生参考转录组，但在人类慢性HIV和SIV感染的背景下，RM，SM和AGM。 我们认为，这些资源的潜在影响是巨大的。资源应用程序包括：（i）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，（ii）开发工具（例如，物种特异性基因探针或微阵列）用于艾滋病相关的系统生物学研究;（iii）调查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.