Transcriptome resources for comparative primate models of lentivirus infection

慢病毒感染比较灵长类动物模型的转录组资源

• 批准号: 8714090
• 负责人: Guido Silvestri
• 金额: $ 74.04万
• 依托单位: EMORY UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-08-05 至 2017-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8714090
• 关键词: AIDS prevention; Acquired Immunodeficiency Syndrome; Acute; Animals; Atlases; Basic Science; Bioinformatics; Blood; Cell model; Cells; Cercocebus atys; Cercopithecus pygerythrus; Cessation of life; Chronic; Chronic Phase; Clinical Research; Collection; Communities; Comparative Study; Data Set; Databases; Experimental Designs; Gene Expression Profile; Genes; Genome; Goals; HIV; HIV therapy; HIV-1; Human; Immune; Immune response; Immune system; In Vitro; Infection; Inflammation; Investigation; Lentivirus Infections; Letters; Light; Macaca mulatta; Medical; Messenger RNA; Modeling; Molecular; Monoclonal Antibody R24; Outcome; Pan Genus; Pathogenesis; Phenotype; Population; Prevention; Primate Lentiviruses; Primates; Principal Investigator; Process; RNA; Research; Research Personnel; Resources; SIV; Sampling; Sorting - Cell Movement; Subfamily lentivirinae; Systems Biology; Therapeutic; Time; Tissues; Translational Research; Viral Load result; Viremia; Virus Diseases; Virus Replication; antiretroviral therapy; cell type; comparative; design; experience; immune activation; immunopathology; in vivo; next generation sequencing; nonhuman primate; novel; pandemic disease; public health relevance; repository; research study; response; tool development; transmission process; web site

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.

描述（由申请人提供）：该R24应用程序的目的是为基线和HIV和SIV感染期间的几种免疫细胞类型生成整个转录组参考数据库，重点是致病性和非致病感染的比较模型。我们设想这些数据库将作为研究艾滋病发病机理，预防和治疗学研究的新颖而宝贵的资源。该项目是与下一代测序相关的革命进步的产物，并利用了Katze博士在系统生物学和生物信息学方面的互补专业知识以及艾滋病研究中的Silvestri博士。 在AIM 1中，我们将在四种灵长类动物（人类，恒河猕猴，RMS，烟草，SMS，SMS和非洲绿色猴子，AGM，AGMS）中生成几个关键免疫细胞亚集（“免疫”）的基线参考转录组。我们将从每个物种中对细胞类型进行分类，并将分离由Katze Lab进行全面测序的RNA。在AIM 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模型中的急性SIV感染中。在AIM 3中，我们将为相同的免疫细胞生成参考转录组，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：（i）对已经测序物种的基因模型的改进以及新物种的基因组组装/注释的帮助（即SMS和AGMS）； （ii）开发与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）研究急性干旱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生成新的假设，设计新的实验，并在HIV预防和治疗领域进行基本，转化和临床研究。