IMMUNOLOGICAL AND VIROLOGICAL EVENTS IN EARLY HIV INFECTION

描述（由申请人提供）：本竞争性更新申请的首要目标是了解急性HIV-1感染期间和之后宿主免疫力与病毒复制、进化和适应性之间的相互作用。我们的工作目标是加强控制和预防感染。对这项工作的前5年的支持非常富有成效，产生了对早期感染宿主-病原体动力学的重要见解，由于免疫逃逸而发生的对病毒适应性的影响，HIV-1暴露个体中保持血清阴性的病毒的动力学和细胞部位，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。我们的项目是独一无二的，因为我们专注于对急性HIV-1 B感染时入组的受试者进行深入、多方面的分析，然后纵向随访多年。我们对供体-受体伴侣对和病毒适应性的额外关注代表了这些领域的最先进领导力。在这次更新中，我们增加了一个新的项目和新的评估层面，即最初的艾滋病毒不一致夫妇和随后的异性性传播，包括艾滋病毒1亚型A、C和D。我们的研究对于继续加深我们对原发性艾滋病毒感染的理解和设计保护性艾滋病毒疫苗至关重要。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，进一步剖析宿主控制的生物机制。我们的计划是由三个项目组成，结合联合收割机的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、病毒学和储存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.