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: 6725462
• 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/6725462
• 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.

鉴定携带低水平HIV-1的细胞 复制和更新病毒库的患者服用高活性 抗逆转录病毒治疗（HAART）对于提高 抑制疗法虽然CD 4 + T细胞和组织巨噬细胞是潜在的 病毒库，单核细胞在体内HIV-1感染中的作用仍然存在 晦涩难懂。最近的研究表明，除了 静息CD 4 + T细胞。我们最近的研究表明， 在存在HAART的情况下，在体内CD 14+单核细胞中发生复制， HIV-1在CD 14+单核细胞中的复制是HIV持续感染的重要来源， 接受高效抗逆转录病毒疗法的人中的HIV-1复制。CD 14单核细胞的HIV-1感染 似乎发生在感染后不久。病毒动力学表明 CD 14+单核细胞中的病毒进化速率高于静息CD 4 + T细胞中的病毒进化速率。 在HAART治疗下，活化的CD 4 + T细胞和接近活化的CD 4 + T细胞。的 该提案的目标是扩展我们目前对 CD 14+单核细胞中的HIV-1，并定义CD 14+单核细胞在HIV- 1中的作用 在存在和不存在抗逆转录病毒药物的情况下， 具体目标：1）确定抗逆转录病毒疗法对 体内CD 14+单核细胞中HIV-1复制的动力学; 2）评估 CD 14+单核细胞是HIV- 1复制的主要来源 接受不同的抗逆转录病毒治疗或不接受治疗。这些病毒动力学研究 将以急性感染患者为中心， 延迟治疗，未接受治疗或不连续治疗的患者，以及 接受蛋白酶抑制剂或非蛋白酶抑制剂的患者。结果 从这个建议将提供更好的理解生产性感染的 HIV-1在体内CD 14+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。