IMMUNE REACTIVITY AND ONCOGENIC VIRUS INFECTION

描述：(改编自调查员摘要)组合反 逆转录病毒化疗提供了最有希望的持续治疗方法 抑制HIV-1复制。通过更好地了解交互 在细胞、病毒和药物之间，更有效的组合策略 将发展对HIV-1的长期抑制。本项目的具体目标 包括以下内容：(1)表征宿主细胞因素，例如 它们的激活状态改变了对抗逆转录病毒的反应 组合。(2)确定病毒致病因素，如 抗性基因、合胞体诱导表型或病毒载量 以确定对抗逆转录病毒组合的反应。(3)刻画 感染者抗HIV-1细胞免疫应答的变化 作为对有效的抗逆转录病毒联合疗法的反应。体外模型 系统，如CD4细胞生长试验和病毒突破 复制试验将被用于模拟临床情况，包括 急性感染、潜伏期和持续性生产性感染。静息细胞 与激活的细胞模型相比，将探索淋巴细胞和 单核/巨噬细胞，以开发可在 诊所。个性化的组合策略将在 将监测细胞介导的免疫反应的患者，例如， 细胞毒性T淋巴细胞(CTL)活性，以及病毒载量。减少 在HIV-1中的负载应该通过CTL活性的增加来反映，从而导致 治疗和免疫反应之间的进一步协同作用。通过在体外结合 而体内联合方案的研究认为，最佳方案是 可以为持久的HIV-1开发联合治疗方案 抑制力。

DESCRIPTION: (Adapted from investigator's abstract) Combination anti retroviral chemotherapy offers the most promising approach for sustained suppression of HIV-1 replication. By better understanding interactions among cells, virus and drugs, more effective combination strategies for prolonged HIV-1 inhibition will be developed. Specific aims of this project include the following: (1) To characterize host cellular factors, such as their state of activation, that modify responses to anti retroviral combinations. (2) To characterize viral pathogenetic factors, such as resistance genotype, syncytium-inducing phenotype, or viral load, that help to determine responses to anti retroviral combinations. (3) To characterize changes in anti-HIV-1 cell mediated immune responses in infected individuals in response to potent anti retroviral combination regimens. In vitro model systems, such as the CD4 cell outgrowth assay and the viral breakthrough replication assay will be utilized to mimic clinical conditions including acute infection, latency, and persistent productive infection. Resting cell versus activated cell models will be explored for both lymphocytes and monocyte/macrophages in order to develop strategies that can be tested in the clinic. Individualized combination strategies will be studied in patients who will be monitored for cell-mediated immune responses, e.g., cytotoxic T lymphocyte (CTL) activity, as well as for virus load. Decreases in HIV-1 load should be mirrored by increases in CTL activity, resulting in further synergy between therapy and immune responses. By combining in vitro and in vivo studies of combination regimens, it is believed that optimal therapeutic combination regimens can be developed for durable HIV-1 inhibition.