Characterizing Host-Virus Interactions in a New HIV Model Organism

表征新的 HIV 模型生物中的宿主病毒相互作用

• 批准号: 10548703
• 负责人: Sara Sawyer
• 金额: $ 74.79万
• 依托单位: UNIVERSITY OF COLORADO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-15 至 2027-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10548703
• 关键词: AIDS/HIV problem; Animal Model; Animals; Antibodies; Award; Binding; Biological Assay; Biological Models; Biology; Blood; Bypass; CCR5 gene; CD8-Positive T-Lymphocytes; Capsid; Cells; Cellular Immunity; Characteristics; Clinical Trials; Consequentialism; Cyclophilins; Development; Engineering; Epitopes; Event; Future; Genome; Goals; Grant; HIV; HIV Genome; HIV Infections; HIV vaccine; HIV-1; HIV-1 vaccine; HIV-2; Human; Human body; Immunity; Immunocompetent; Infection; Integration Host Factors; Learning; Lentivirus; Life; Macaca; Minor; Modeling; Modification; Molecular; Monkeys; Mutation; National Institute of Drug Abuse; Night Monkey; Persons; Pharmaceutical Preparations; Physiological; Point Mutation; Primates; Reagent; Research; Serum; T-Lymphocyte Epitopes; TRIM Gene; Testing; Time; Vaccines; Vertebral column; Viral Genome; Virus; Virus Replication; Zoonoses; acute infection; antibody diagnostic; awake; cofactor; cross-species transmission; design; improved; in vivo; insight; pandemic disease; pathogen; receptor; seroconversion; simian human immunodeficiency virus; tool; transmission process; vaccine development; viral transmission; virus host interaction

PROJECT SUMMARY HIV remains the most consequential zoonosis of the last century, with 36 million fatalities and another 37 million infected. Even today, almost 2,000 people per day die of HIV/AIDS globally. Medications are reducing the effects of HIV on the human body and transmission of the virus to others. However, forty years into the HIV/AIDS pandemic, there are still no vaccines or cures. One hindrance to the development of HIV vaccines and cures has been the lack of an effective animal model organism. Macaques were thoughtfully developed as an animal model in the 1980s and remain the main HIV model today. However, there are well-known problems with this model, with the most significant problem being that SHIVs can only be made to contain about 30% of the HIV-1 genome (essentially, just Env). Here, we describe a new animal model for HIV infection. The overarching goal of this grant is to design and test physiologically-relevant transmitted/founder (T/F) HIV-1 strains for this new model species. We examine and optimize the ability of these viruses to bind to CCR5 and RanBP2 host factors in the new model species, and study how the virus is evading restriction factors in this species. All newly developed viruses will then be assayed for their sensitivity to neutralization by HIV-1 antibodies. Taken together, we will learn about the molecular underpinnings of HIV host switching, and at the same time the viruses we design in this proposal will become a vital tool for HIV-1 research. This new animal model will serve as an exciting new model system in which to study all aspects of HIV-1 biology and immunity.

项目概要 艾滋病毒仍然是上世纪最严重的人畜共患病，导致 3600 万人死亡，另有 3700 万人死亡 已感染。即使在今天，全球每天仍有近 2,000 人死于艾滋病毒/艾滋病。药物正在减轻影响 HIV 对人体的影响以及将病毒传播给他人的情况。然而，艾滋病毒/艾滋病流行四十年后 大流行，仍然没有疫苗或治疗方法。艾滋病毒疫苗和治疗方法开发的一大障碍 一直缺乏有效的动物模型生物。猕猴是经过精心培育的动物 20 世纪 80 年代的模型，至今仍然是主要的 HIV 模型。然而，这存在众所周知的问题 模型中，最重要的问题是 SHIV 只能含有约 30% 的 HIV-1 基因组（本质上只是 Env）。在这里，我们描述了一种新的艾滋病毒感染动物模型。总体目标 这笔赠款的一部分是为这种新的设计和测试生理相关的传播/创建 (T/F) HIV-1 毒株 模式物种。我们检查并优化这些病毒与 CCR5 和 RanBP2 宿主因子结合的能力 在新的模型物种中，研究病毒如何逃避该物种的限制因素。全部都是新的 然后将检测开发的病毒对 HIV-1 抗体中和的敏感性。综合起来， 我们将了解艾滋病毒宿主转换的分子基础，同时了解我们所感染的病毒 该提案中的设计将成为 HIV-1 研究的重要工具。这种新的动物模型将作为一个令人兴奋的 新的模型系统，用于研究 HIV-1 生物学和免疫的各个方面。