ROLE OF MONOCYTES IN AIDS AND AS TARGETS FOR ANTIVIRAL THERAPY

单核巨噬细胞是HIV-1的重要宿主，在HIV-1感染中起着关键作用。 病毒的传播和艾滋病的发病机制。 这些研究 专注于定义单核细胞的表型和功能变化 来自AIDS患者的吞噬细胞和HIV-1感染后的正常单核细胞 体外感染。 基于新出现的证据，单核细胞是 艾滋病进化的核心，研究也旨在探索 针对这一人群的潜在抗病毒疗法。 最近的证据 表明体外感染HIV-1的单核细胞分泌TGF-β 1， 此外，HIV-1感染的单核细胞谱系的细胞， 已经在艾滋病患者的组织中发现了产生TGF-β的基因。 鉴定TGF-β，一种具有多种免疫调节作用的细胞因子 HIV-1感染的脑组织中的细胞因子功能暗示了HIV中的这种细胞因子 脑病 此外，HIV-1感染的单核细胞 吞噬细胞产物调节星形胶质细胞功能的作用 一旦单核细胞到达中枢神经系统， 艾滋病的脑内病理特征的延续。 由于单核吞噬细胞在HIV感染中的作用， 针对这一人群使用抗病毒药物。 在这 在这方面，IL-2-毒素融合缀合物已显示选择性结合 HIV感染的IL-2受体阳性单核细胞，从而消除这种 人口 持续研究以阐明表型和功能 这些细胞的异常可能提供新的治疗途径。

Mononuclear phagocytes are important hosts for HIV-1, playing key roles in the dissemination of the virus and the pathogenesis of AIDS. These studies focus on defining phenotypic and functional changes of mononuclear phagocytes from AIDS patients and in normal monocytes following HIV-1 infection in vitro. Based on the emerging evidence that monocytes are central to the evolution of AIDS, studies are also directed at exploring potential antiviral therapies targeted at this population. Recent evidence indicates that monocytic cells infected with HIV-1 in vitro secrete TGF- beta and furthermore, HIV-1 infected cells of monocytic lineage which produce TGF-beta have been identified in tissues of AIDS patients. Identification of TGF-beta, a cytokine with numerous immunoregulatory functions in HIV-1-infected brain tissues implicates this cytokine in HIV encephalopathy. Moreover, the ability of HIV-1 infected mononuclear phagocyte products to modulate astrocyte functions suggests a pivotal role for the monocytic cells once they reach the CNS both in the initiation and perpetuation of the intracerebral pathology characteristic of AIDS. Because of the role of mononuclear phagocytes in HIV infection, studies were undertaken to target antiviral agents to this population. In this regard, an IL-2-toxin fusion conjugate has been shown to selectively bind to HIV-infected, IL-2 receptor positive monocytes, thereby eliminating this population. Continuing studies to elucidate phenotypic and functional abnormalities in these cells may provide new avenue of therapy.