Duke Center for HIV Structural Biology

杜克大学艾滋病毒结构生物学中心

基本信息

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
项目类别：
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

项目摘要

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4000万人患有艾滋病毒/艾滋病；但是，受保护的疫苗或功能治愈仍然是难以捉摸的任务四十年的深入研究。 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。拟议的杜克艾滋病毒中心结构生物学将为HIV-1进入和融合的动态提供新的见解膜，ENV引起的B细胞受体的免疫反应以及抗ENV抗体在阻止病毒反弹。该中心将进行旨在1）建立完整的时间的结构研究 HIV-1环境融合的解决且原子上详细的机制； 2）用自体（ANAB）和广泛中和抗体（BNAB）的特异性； 3）要达到原子水平了解抗体介导的对潜在HIV-1储层反弹的控制。这些的最终目标研究是为了推进结构生物学技术和HIV-1 Env结构衍生疾病的知识 HIV-1感染和反弹中的机制。此外，通过其发展核心，该中心将为追求的早期职业调查人员和学员提供资源和培训机会 HIV-1结构生物学领域的职业。