Non-Human Primate and Imaging Core

摘要-核心B：非人灵长类和成像核心 HIV治愈的一个主要障碍是构成病毒库的HIV-1感染细胞的持久性。而当 目前的抗逆转录病毒联合疗法能够将病毒复制抑制到低于检测到的水平(50 在患者的血浆中，ART的停止几乎总是会导致病毒的死灰复燃，即使在患者 ART是在感染后早期启动的。这导致了冲击和杀戮方法的形成 使用ART保护伞下的潜伏期反转剂来激活和减少储液器，尽管这样 到目前为止，在没有免疫治疗的情况下，这种方法还没有产生任何临床益处。然而，这些结果 清楚地表明，长期持续的艾滋病毒宿主在感染后迅速播种，这一点得到证实 HIV的非人灵长类模型。此外，来自几个组织和我们的数据强烈表明，残留物 病毒复制实际上是在各种淋巴组织中进行的，尽管ART非常活跃，尽管它是由于 药物渗透、转化或抗病毒免疫贡献有限的庇护所。在此应用程序中，我们 建议量化和绘制阴道感染和早期ART干预后早期水库形成的地图， 使用一系列最先进的成像技术以及对储集层的详细细胞分析 在不同的艺术启蒙时期获得。接下来，我们建议解决以下功能储油层 延长ART和ART中断，监测组织中残留的病毒复制，早期病毒部位 反弹，活性储存库的细胞来源和旨在增强抗病毒作用的免疫干预 导致抗病毒控制的反应。

Summary - Core B: Non-human Primate and Imaging Core A major barrier to HIV cure is the persistence of HIV-1 infected cells that constitute the viral reservoir. While current antiretroviral combination therapies are able to inhibit viral replication to below detectable levels (50 copies) in the plasma of patient, ART cessation almost invariably leads to viral resurgence even in patients for which ART was initiated early post infection. This has led to the formulation of Shock and Kill approaches to activate and reduce the reservoirs using latency reversing agents under the umbrella of ART, though such approach in the absence of immunotherapy has not had any clinical benefit thus far. However, these results clearly indicate that long-term persistent HIV reservoirs are seeded rapidly post infection as confirmed it the nonhuman primate model of HIV. In addition, data from several groups and ours strongly suggest that residual viral replication is actually ongoing in various lymphoid tissues in spite of highly active ART, be it due to poor drug penetration, conversion or sanctuaries with limited antiviral immune contribution. In this application, we propose to quantify and map the early reservoir formation after vaginal infection and early ART intervention, using a series of state of the art imaging techniques as well detailed cellular analyses of the reservoirs obtained at various times of ART initiation. Next we propose to address the functional reservoir following prolonged ART and ART interruption, monitoring residual viral replication in tissues, sites of early viral rebound, the cellular origin of the active reservoir and immune interventions designed to bolster antiviral responses leading to antiviral control.