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: 6873704
• 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 2007-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6873704
• 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 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）对于提高治疗效率非常重要 抑制疗法。虽然 CD4+ T 细胞和组织巨噬细胞具有潜力 病毒储存库，单核细胞在体内 HIV-1 感染中的作用仍然存在 朦胧。最近的研究表明，除了病毒之外，还存在其他病毒来源 静息 CD4+ T 细胞。我们最近的研究表明，持续的 HIV-1 在HAART存在的情况下，CD 14+单核细胞体内发生复制，并且 HIV-1 在 CD 14+ 单核细胞中的复制是持久性感染的重要来源 HIV-1 在接受 HAART 治疗的人群中复制。 CDI 4 单核细胞的 HIV-I 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 CD4+ T 中的病毒进化速率 细胞并接近 HAART 治疗下活化的 CD4+ T 细胞。这 该提案的目标是扩展我们目前对动态的理解 CD14+ 单核细胞中的 HIV-1，并定义 CD 14+ 单核细胞在 HIV-1 中的作用 在存在或不存在抗逆转录病毒药物的情况下，由以下因素引起的感染 具体目标： 1) 确定抗逆转录病毒治疗对 HIV-1在体内CD14+单核细胞中复制的动态； 2）评估是否 CD14+单核细胞是患者体内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抗逆转录病毒治疗。这些病毒动力学研究 将以早期接受治疗的急性感染患者为中心 延迟治疗、未接受治疗或间断治疗的患者，以及 接受蛋白酶抑制剂或非蛋白酶抑制剂的患者。发现 该提案将有助于更好地理解生产性感染 体内 CD 14+ 单核细胞中的 HIV-1，也可能为以下方面提供重要见解： 开发新的治疗策略以提高治疗效果。

项目成果

Blood monocytes harbor HIV type 1 strains with diversified phenotypes including macrophage-specific CCR5 virus.

• DOI: 10.1086/524847
• 发表时间: 2008-01
• 期刊: The Journal of infectious diseases
• 作者: Younong Xu;Haiying Zhu;Carrie K. Wilcox;A. V. van’t Wout;Thomas Andrus;N. Llewellyn;L. Stamatatos;J. Mullins;L. Corey;Tuofu Zhu