Duke Center for HIV Structural Biology

杜克大学艾滋病毒结构生物学中心

• 批准号: 10643906
• 负责人: Priyamvada Acharya
• 金额: $ 548.85万
• 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/10643906
• 关键词: Acquired Immunodeficiency Syndrome; Adherence; Antibodies; Autologous; B-Cell Activation; B-Cell Antigen Receptor; B-Cell Receptor Binding; B-Lymphocytes; Behavior; Binding; Biology; Blocking Antibodies; Cell membrane; Cells; Chronic Disease; Clinical; 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; HIV/AIDS; Immune; Immune Evasion; Immune response; Immune system; Immunobiology; Immunoglobulin Fragments; 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; Visualization; antiretroviral therapy; atomic interactions; career; env Glycoproteins; 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年深入研究，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进化。拟议中的杜克艾滋病中心 结构生物学将为HIV-1进入和与宿主融合的动力学提供新的见解 膜，Env启动的B细胞受体的免疫激活，以及抗Env抗体在 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 HIV-1 Env融合的解析和原子详细机制; 2）定义BCR复合物结构， 自体抗体（anAb）和广泛中和抗体（bnAb）的特异性;和3）达到原子水平 了解抗体介导的HIV-1潜伏宿主反弹控制。这些项目的最终目标 研究的目的是推进HIV-1 Env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 提供资源和培训机会，为早期职业调查人员和学员谁追求 HIV-1结构生物学领域的研究