Immunology and Virology of Acute HIV Infection

描述(由申请人提供)：拟议的西雅图初级感染计划(SeaPIP)的总体目标将是定义急性HIV-1感染的特征，这对在控制HIV-1感染方面赋予长期优势非常重要。将利用最先进的免疫学和病毒学技术来识别宿主控制的生物学机制。我们的免疫学项目将专注于识别病毒特异性免疫反应，因为它们在新感染的宿主中发展，以及与病毒学控制相关的免疫反应的效应细胞。提出了两个病毒学项目。其中一个将确定宿主强加的病毒基因组选择的最早目标，HAART下的感染库，以及治疗和宿主反应对HIV-1感染的这一残留核心的影响。第二个病毒学项目将确定病毒感染过程中发生的突变变化对不同宿主细胞环境中病毒适合性的影响。我们将进一步整合这些研究，将宿主免疫反应和病毒学特性定义为以下函数：感染时间，感染后开始治疗的时间，以及在治疗中断或中断时检测到的T细胞变化和病毒反弹。在初级艾滋病毒感染领域拥有长期合作记录的高级调查人员已经聚集在一起，将尖端的免疫学、病毒学和生物信息学技术与临床观察相结合。 为了支持这些努力，该计划将包括一个经验丰富的临床核心，它将启动一项积极的招募工作，重点是在艾滋病毒感染的最早阶段招募新患者，并继续监测我们的初级感染诊所(PIC)队列中积极跟进的143名患者中的25名高优先级子集。病毒学核心将负责接收和存储样本、样本处理、组织培养中的病毒分离、病毒载量测量和耐药性突变测试。最后，行政核心将负责协调方案各组成部分之间的持续互动，包括促进科学协调、数据和样本管理、财政监督和支持法规遵从性，以及为所有项目和核心提供统计支持。

DESCRIPTION (provided by applicant): The overall goal of the proposed Seattle Primary Infection Program (SeaPIP) will be to define features of acute HIV-1 infection important to conferring a long-term advantage in controlling HIV-1 infection. State-of-the-art immunologic and virologic technologies will be brought to bear to discern biological mechanisms underlying host control. Our immunology project will be focused on identifying virus-specific immune responses as they develop in the newly infected host, and the effector cells of the immune response that correlate with virologic control. Two virology projects are proposed. One will identify the earliest targets of host-imposed viral genome selection, the reservoirs of infection under HAART, and the influence of therapies and host responses on this residual core of HIV-1 infection. The second virology project will define the impact of mutational changes that occur in the viral infection process on viral fitness in different host cell environments. We will further integrate these studies by defining host immune responses and virologic properties as functions of the following: time of infection, the time post-infection that therapy is initiated, and the T cell changes and viral rebound detected upon interruption or discontinuation of therapy. Senior investigators with long-term collaborative records in the field of primary HIV infection have been assembled to integrate cutting edge immunological, virologic and bioinformatics technologies with clinical observations. In support of these efforts, the program will include an experienced Clinical Core that will mount an aggressive recruitment effort focusing on new enrollment of patients in the earliest stages of HIV infection, as well as continue to monitor a high priority subset of 25 of the 143 patients in active follow-up in our Primary Infection Clinic (PIC) Cohort. A Virology Core will be responsible for receiving and storing specimens, specimen processing, virus isolation in tissue culture, viral load measurements, and drug resistance mutation testing. Lastly, an Administrative Core will function to coordinate continuous interactions between the program components, including facilitating scientific coordination, data and specimen management, fiscal oversight, and support for regulatory compliance, as well as providing statistical support for all Projects and Cores.