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.

项目摘要 艾滋病毒仍然是上个世纪最结果的人畜共患病，死亡人数为3600万，还有3700万 已感染。即使在今天，全球每天近2,000人死于艾滋病毒/艾滋病。药物正在减少影响 艾滋病毒在人体上的艾滋病毒和病毒传播给他人。但是，艾滋病毒/艾滋病四十年 大流行，仍然没有疫苗或治疗方法。艾滋病毒疫苗和治疗的一种障碍 一直缺乏有效的动物模型生物。猕猴是作为动物的经过深思熟虑的 模型在1980年代，仍然是当今主要的HIV模型。但是，有很多问题 模型，最重要的问题是只能使SHIV仅包含大约30％的HIV-1 基因组（本质上，只是环境）。在这里，我们描述了一种新的HIV感染动物模型。总体目标 这项赠款的是设计和测试与生理相关的传播/创建者（T/F）HIV-1菌株 模型物种。我们检查并优化了这些病毒与CCR5和RANBP2宿主因子结合的能力 在新的模型物种中，并研究该病毒如何在该物种中逃避限制因素。全部 然后，将分析开发的病毒对HIV-1抗体对中和的敏感性进行测定。在一起， 我们将了解HIV宿主转换的分子基础，同时我们的病毒 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成为一个令人兴奋的 研究HIV-1生物学和免疫力的各个方面的新模型系统。