IMMUNOLOGICAL AND VIROLOGICAL EVENTS IN EARLY HIV INFECTION

描述(由申请人提供)：这一竞争性续签申请的首要目标是了解宿主免疫与病毒复制、进化和适应性之间的相互作用，在急性HIV-1感染期间和之后。我们的工作目标是加强感染控制和预防。对这项工作的头5年的支持非常有成效，对早期感染宿主-病原体动态、免疫逃逸对病毒适合性的影响、血清阴性的HIV-1暴露个体中病毒的动态和细胞位置、治疗干预以及在制定最先进的疫苗免疫原设计中使用这些数据产生了重要的见解。我们的计划的独特之处在于，我们专注于对在急性HIV-1B感染期间登记的受试者进行深入的、多方面的分析，然后进行多年的纵向跟踪。我们对捐赠者-接受者伴侣对和病毒适合性的额外关注代表了这些领域的最新领先地位。在这次更新中，我们增加了一个新的项目和对最初艾滋病毒不和谐的夫妇和随后涉及艾滋病毒-1亚型A、C和D的异性传播进行评估的新方面。我们的研究对于继续我们对初级艾滋病毒感染的日益增长的了解和保护性艾滋病毒疫苗的设计至关重要。在三个高度互动的研究项目中，将利用最先进的免疫学、遗传学和病毒学技术来进一步剖析宿主控制的生物学机制。我们的计划由三个项目组成，这三个项目结合了病毒进化和适应宿主免疫遗传学和细胞免疫反应的领域。我们还有四个核心，涵盖行政、临床、病毒学和资料库以及生物统计职能的基本要素。

DESCRIPTION (provided by applicant): The overriding goals of this competing renewal application are to understand the interactions between host immunity and viral replication, evolution and fitness, during and beyond acute HIV-1 infection. Our work is targeted to the goals of enhancing control and prevention of infection. The first 5 years of support for this work have been very productive, yielding important insight into early infection host-pathogen dynamics, the impact on viral fitness that occurs as a result of immune escape, the dynamics and cellular site of virus in HIV-1 exposed individuals that remain seronegative, therapeutic interventions, and the use of this data in the formulation of state-of-the-art vaccine immunogen designs. Our program is unique in that we focus on in-depth, multifaceted analysis of subjects that were enrolled while in acute HIV-1 B infection and then followed longitudinally for many years. Our additional foci on donor-recipient partner pairs and viral fitness represent state of the art leadership in these areas. In this renewal, we have added a new Project and the new dimension of evaluation of initially HIV-discordant couples and subsequent heterosexual transmission involving HIV-1 subtypes A, C and D. Our studies are critically important to the continuation of our growing understanding of primary HIV infection and to the design of protective HIV vaccines. State-of-the-art immunological, genetic and virologic technologies will be brought to bear to further dissect the biological mechanisms underlying host control, in three highly interactive research projects. Our Program is composed of three Projects that combine the areas of viral evolution and adaptation to host immunogenetics and cellular immune responses. We also have four Cores, covering the essential elements of Administration, Clinical, Virological and Repository, and Biostatistics functions.