MODULATION OF HIV-1 REPLICATION BY CYTOKINES AND SOLUBLE CYTOKINE RECEPTORS

细胞因子和可溶性细胞因子受体对 HIV-1 复制的调节

• 批准号: 6161280
• 负责人: K. A CLOUSE-STREBEL
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/6161280
• 关键词: T lymphocyte; cytokine; cytokine receptors; gene induction /repression; human immunodeficiency virus 1; human tissue; interleukin 4; macrophage; monocyte; nuclear factor kappa beta; oxidative stress; selenium; tissue /cell culture; transcription factor; tumor necrosis factor alpha; virus replication

Cytokines are cell-derived proteins that function as hormones in the immune system and affect cellular growth and differentiation. Their effects on human cells enable cytokines to modulate replication of HIV-1. We are determining the effects of various cytokines on HIV replication in lymphocytes and monocytes, cells involved in the immune response and also susceptible to infection with HIV. Since the ability to control cytokine-mediated modification of HIV replication is important therapeutically, we are studying the ability of natural antagonists to control modulation of HIV replication by cytokines. We have shown that replication of HIV in human cells can be induced by the cytokine, TNF-a, and that this induction can be reversed by using soluble TNF receptors. We now find that selenium can modulate TNF effects on HIV replication in chronically infected MO and T cells, but only on acute infection of MO. We also find that IFN-a species/components vary in their ability to inhibit HIV replication, which may facilitate selection of a less toxic IFN-a that can be used in vivo. The work ongoing in my laboratory is directed at understanding how existing networks involving cytokines and/or their soluble receptors function in vitro and in vivo. An understanding of this mechanism allows for a more detailed and scientific approach to the review of new products, both cytokines and soluble cytokine receptors, proposed for therapeutic use as antagonists to cytokine activity in vivo. Since my laboratory has shown that a delicate balance exists between cytokines and their antagonists, such that both enhancement and inhibition of cytokine biologic activity can result by altering their concentrations, it sheds new light on the complexities that exist for the proposed therapeutic use of these agents. Our findings may also assist in determining what parameters to monitor in patients that are receiving either cytokines or soluble cytokine receptors.

细胞因子是细胞来源的蛋白质，其在细胞内起激素的作用。 免疫系统并影响细胞生长和分化。 他们的 对人类细胞的作用使得细胞因子能够调节HIV-1的复制。 我们正在确定各种细胞因子对HIV复制的影响， 淋巴细胞和单核细胞，参与免疫应答的细胞， 容易感染艾滋病病毒。 因为控制的能力 苦参碱介导的HIV复制修饰很重要 在治疗上，我们正在研究天然拮抗剂的能力， 通过细胞因子控制HIV复制的调节。 我们已经证明 HIV在人细胞中的复制可由细胞因子TNF-α诱导， 并且这种诱导可以通过使用可溶性TNF受体来逆转。 我们现在发现硒可以调节TNF对HIV复制的影响， 慢性感染的MO和T细胞，但仅对急性感染的MO。 我们还发现，IFN-α种类/组分在它们的能力上是不同的， 抑制HIV复制，这可能有助于选择毒性较小的 可以在体内使用的IFN-α。 我的实验室正在进行的工作旨在了解 涉及细胞因子和/或其可溶性受体的现有网络 在体外和体内发挥作用。 对这种机制的理解， 以更详细和科学的方法审查新的 产品，细胞因子和可溶性细胞因子受体，提出用于 作为体内细胞因子活性拮抗剂的治疗用途。 自从我 实验室已经表明，细胞因子之间存在微妙的平衡， 它们的拮抗剂，使得细胞因子的增强和抑制 生物活性可以通过改变它们的浓度来产生，它会释放 新的光存在的复杂性，为拟议的治疗用途 这些代理人。 我们的发现也可能有助于确定 在接受细胞因子的患者中监测的参数， 可溶性细胞因子受体