Doctoral Dissertation Improvement: Primate Innate Immune Defense and Adaptation to SIV/HIV Infection

博士论文改进：灵长类动物先天免疫防御和对SIV/HIV感染的适应

• 批准号: 0648457
• 负责人: Todd Disotell
• 金额: $ 0.9万
• 依托单位: New York University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-01-01 至 2007-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=0648457&HistoricalAwards=false
• 关键词: Doctoral; Dissertation; Improvement; Primate; Innate

Viruses have been part of the primate environment for tens of thousands to millions of years and differences in primate susceptibility to viral infection and disease suggests that some species are better adapted to co-exist with certain viruses.? One of the best-known examples of this is variation in primate susceptibility to simian (or human) immunodeficiency viruses (SIV/HIV) and AIDS-like diseases.? Despite a high level of genetic similarity among primate species, the same viruses that have been known to cause AIDS in humans (SIV/HIV) are generally non-pathogenic in most naturally infected non-human primates.? This research hypothesizes that there is key variation in the primate innate immune system that leads to the observed variation in susceptibility.In order to determine if specific innate immune system genes contribute to SIV/HIV pathogenicity in primates, the protein-coding regions of ten genes involved in one of two viral recognition pathways (TLR7/ssRNA induced signaling pathway and RIG-I/dsRNA induced signaling pathway) will be sequenced in 18 primate species.? Species were chosen to represent taxa with varying degrees of relatedness and susceptibility to SIV/HIV infection and AIDS-like diseases.There are three main objectives to this research.? Objective 1 is to test for signs of adaptation by comparing immune system gene trees to species phylogenies.? Objective 2 is to test for signs of adaptation by looking for signatures of positive and negative selection across loci and species. Objective 3 is to test the functional significance of these adaptations by mapping variable amino acids to particular binding domains on the translated protein.This research will further our understanding of the evolution of the primate immune system and determine if variation in theses genes contribute to variation in a primate species? ability to co-exist with SIV infection.? More generally, the project will serve as a model for understanding molecular co-adaptation by examining interactions between an organism?s innate immune system and viruses and may be useful for biomedical research attempting to combat HIV/AIDS in humans by providing potential targets for drug development.?This doctoral dissertation improvement project will serve as the co-investigator?s thesis research and result in her being trained in state-of-the-art molecular, analytical, and bioinformatics techniques. This research will be published as a dissertation and in scholarly papers, as well as presented at academic conferences.? Sequences generated as part of this research will be annotated and submitted to GenBank.

病毒已经成为灵长类动物环境的一部分，数以百万到数百万年，而灵长类动物对病毒感染的敏感性和疾病的敏感性差异表明，某些物种更好地适应了与某些病毒共存。最著名的例子之一是灵长类动物易感性的变化，对邻肌（或人类）免疫缺陷病毒（SIV/HIV）和类似艾滋病的疾病。尽管灵长类动物之间的遗传相似程度很高，但已知会引起人类辅助的相同病毒（SIV/HIV）在大多数自然感染的非人类灵长类动物中通常是非致病性的。这项研究假设，灵长类动物先天免疫系统的关键变化导致观察到的易感性变化。途径）将在18种灵长类动物中进行测序。选择物种代表具有不同程度的相关性和对SIV/HIV感染和类似艾滋病疾病的易感性的分类单元。这项研究有三个主要目标。目标1是通过将免疫系统基因树与物种系统发育进行比较来测试适应的迹象。目标2是通过寻找基因座和物种的正选择标志来测试适应的迹象。目标3是通过将可变氨基酸映射到翻译蛋白上的特定结合结构域来测试这些适应的功能意义。这项研究将进一步了解我们对灵长类动物免疫系统的演变的理解，并确定这些基因的变化是否有助于灵长类动物的变化？能够与SIV感染并存。 More generally, the project will serve as a model for understanding molecular co-adaptation by examining interactions between an organism?s innate immune system and viruses and may be useful for biomedical research attempting to combat HIV/AIDS in humans by providing potential targets for drug development.?This doctoral dissertation improvement project will serve as the co-investigator?s thesis research and result in her being trained in state-of-the-art molecular, analytical,和生物信息学技术。这项研究将作为论文和学术论文发表，并在学术会议上发表。作为这项研究的一部分生成的序列将被注释并提交给GenBank。