Duke Center for HIV Structural Biology

杜克大学艾滋病毒结构生物学中心

• 批准号: 10506661
• 负责人: Priyamvada Acharya
• 金额: $ 550.51万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-06-14 至 2027-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10506661
• 关键词: AIDS/HIV problem; Acquired Immunodeficiency Syndrome; Adherence; Antibodies; Autologous; B-Cell Activation; B-Cell Antigen Receptor; B-Lymphocytes; Behavior; Biology; Cell membrane; Cells; Chronic Disease; Clinical Management; Clonal Expansion; Complex; Development; Disease; Disease remission; Economic Burden; Elements; Epitopes; Evolution; Fab Immunoglobulins; Glycoproteins; Goals; HIV; HIV Envelope Protein gp120; HIV Infections; HIV-1; Immune; Immune response; Immune system; Immunobiology; Immunoglobulin Somatic Hypermutation; Individual; Infection; Kinetics; Knowledge; Mediating; Membrane; Methods; Molecular Conformation; Movement; Outcome; Pathway interactions; Peptides; Persons; Play; Process; Proviruses; Receptor Activation; Receptor Signaling; Research; Research Personnel; Resolution; Resources; Role; Series; Signal Pathway; Signal Transduction; Specificity; Structure; Surface; Techniques; Therapeutic; Time; Vaccination; Vaccines; Viral; Viral reservoir; Viremia; Virus; antiretroviral therapy; atomic interactions; career; global health; immune activation; innovation; insight; latent HIV reservoir; molecular dynamics; multilevel analysis; neutralizing antibody; new therapeutic target; pandemic disease; prevent; receptor; receptor binding; resistance mechanism; response; structural biology; temporal measurement; therapeutic target; training opportunity; vaccine development; vaccine response; vaccine trial; viral rebound

Abstract – Overall Approximately 40 million people worldwide are living with HIV/AIDS; however, a protective vaccine or functional cure remain elusive despite four decades of intense research. HIV-1 evades the immune system through its rapid structural evolution during infection and replication. The proposed Duke Center for HIV Structural Biology will provide new insights into the dynamics of HIV-1 entry and fusion with the host membrane, the Env-initiated immune activation of B-cell receptors, and the role of anti-Env antibodies in blocking viral rebound. The Center will pursue structural studies that aim to 1) to develop a complete, time resolved and atomically detailed mechanism of HIV-1 Env fusion; 2) to define BCR complex structures with specificity of autologous (anAb) and broadly neutralizing antibodies (bnAb); and 3) to achieve an atomic level understanding of antibody-mediated control of rebound from latent HIV-1 reservoirs. The ultimate goal of these studies is to advance structural biology techniques and knowledge of HIV-1 Env structure-derived disease mechanisms in HIV-1 infection and rebound. Additionally, through its Developmental Core, the Center will provide resources and training opportunities for early career investigators and trainees who are pursuing careers in the field of HIV-1 structural biology.

摘要--总体 全世界约有4000万人感染艾滋病毒/艾滋病；然而，保护性疫苗或 尽管进行了40年的紧张研究，但功能性治愈仍然难以捉摸。HIV-1逃避免疫系统 通过其在感染和复制过程中的快速结构演变。拟建的杜克艾滋病毒中心 结构生物学将为HIV-1进入和与宿主融合的动态提供新的见解 膜、Env启动的B细胞受体免疫激活以及抗Env抗体在血管内皮细胞瘤中的作用 阻止病毒反弹。该中心将进行结构研究，旨在1)开发一个完整的，时间 解析和原子详细的HIV-1 env融合机制；2)确定BCR复杂结构 自身抗体(Anab)和广谱中和抗体(BNab)的特异性；以及3)达到原子水平 了解抗体介导的控制潜伏的HIV-1储备库的反弹。这些项目的最终目标是 研究是推进HIV-1环境结构衍生疾病的结构生物学技术和知识 HIV-1感染和反弹的机制。此外，通过其发展核心，该中心将 为从事早期职业研究的人员和实习生提供资源和培训机会 HIV-1结构生物学领域的职业。