Role of CD14+ Monocytes in HIV-1 Infection

CD14 单核细胞在 HIV-1 感染中的作用

• 批准号: 6632388
• 负责人: TUOFU ZHU
• 金额: $ 26.6万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-05-01 至 2006-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6632388
• 关键词: AIDS therapy; CD14 molecule; HIV envelope protein; HIV infections; antiAIDS agent; helper T lymphocyte; human subject; macrophage; monocyte; patient oriented research; virus replication

Identification of cells carrying out low-levels of HIV-1 replication and renewing viral reservoirs in patients taking highly active antiretroviral therapy (HAART) is important for enhancing the efficiency of suppressive therapy. While CD4+ T cells and tissue macrophages are potential viral reservoirs, the roles of monocytes in HIV-1 infection in vivo remain obscure. Recent studies suggest the existence of other sources of virus besides resting CD4+ T cells. Our recent studies indicate that ongoing HIV- 1 replication occurs in vivo in CD 14+ monocytes in the presence of HAART, and that HIV-1 replication in CD 14+ monocytes is an important source of persistent HIV-1 replication among persons on HAART. HIV- I infection of CDI 4 monocytes appears to occur shortly after acquisition of infection. Viral dynamics suggest a rate of viral evolution is higher in CD 14+ monocytes than in resting CD4+ T cells and approaches that of activated CD4+ T cells under HAART therapy. The goal of this proposal is to extend our current understanding of the dynamics of HIV-1 in CD14+ monocytes, and to define the roles of CD 14+ monocytes in HIV- 1 infection in the presence and absence of antiretroviral drugs by the following specific aims: 1) to determine the impact of antiretroviral therapy on the dynamics of HIV-1 replication in CD14+ monocytes in vivo; 2) to evaluate if CD14+ monocytes are the major sources of HIV- 1 replication in patients receiving different or no antiretroviral therapy. These viral dynamic studies will be centered around acutely infected patients who received early versus delayed therapy, those who received no therapy or discontinuous therapy, and those who received protease inhibitors, or nonprotease inhibitors. Findings from this proposal will provide better understanding of productive infection of HIV-1 in CD 14+ monocytes in vivo, and may also provide great insights to developing new therapeutic strategies to enhance therapy efficacy.

携带低水平HIV-1的细胞的鉴定 服用高活性药物的患者体内病毒库的复制和更新 抗逆转录病毒治疗(HAART)对于提高人类免疫缺陷病毒的治疗效率非常重要。 抑制性治疗。而CD4+T细胞和组织巨噬细胞是潜在的 病毒库，单核细胞在体内感染HIV-1中的作用仍然存在 默默无闻。最近的研究表明，除了病毒之外，还有其他来源的病毒 静息的CD4+T细胞。我们最近的研究表明，正在进行的HIV-1 在HAART存在的情况下，CD14+单核细胞在体内发生复制，并且 HIV-1在CD14+单核细胞中的复制是持续性的重要来源 在接受HAART治疗的人中复制HIV-1。CDI-4单核细胞感染HIV-I的研究 似乎发生在感染后不久。病毒动力学表明 CD14+单核细胞的病毒进化速度高于静止的CD4+T细胞 细胞和接近于HAART治疗下活化的CD4+T细胞。这个 这项提议的目标是扩大我们目前对动态的理解 CD14+单核细胞表达HIV-1，并探讨CD14+单核细胞在HIV-1中的作用 在有和没有抗逆转录病毒药物的情况下由下列人员感染 具体目标：1)确定抗逆转录病毒治疗对 HIV-1在CD14+单核细胞体内复制的动态；2)评估 CD14+单核细胞是患者HIV-1复制的主要来源 接受不同的或不接受抗逆转录病毒治疗。这些病毒动态研究 将以早期接种的急性感染患者为中心，而不是 延迟治疗，那些没有接受治疗或不连续治疗的人，以及 那些接受了蛋白酶抑制剂或非蛋白酶抑制剂的患者。发现 将提供对产生性感染的更好的理解 HIV-1在体内CD14+单核细胞中的表达，也可能为 开发新的治疗策略，以提高治疗效果。