Inhibition of HIV at the Immune Synapse Utilizing Novel Ligands and Receptors

利用新型配体和受体抑制免疫突触中的 HIV

• 批准号: 7683286
• 负责人: JEROME E GROOPMAN
• 金额: $ 85万
• 依托单位: BETH ISRAEL DEACONESS MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-05 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7683286
• 关键词: AIDS/HIV problem; Anatomic Sites; Antigen-Antibody Complex; Biological; Cannabinoids; Cells; Complex; HIV; HIV Infections; Immune; Ligands; Lymphatic; Research; Surface; Synapses; System; Therapeutic; Virus; cannabinoid receptor; drug abuser; innovation; novel; receptor; transmission process

DESCRIPTION (provided by applicant): Recent research reveals that HIV infection is established within complexes of immune cells termed the "immune synapse." These immune units efficiently pass virus to uninfected cells and promote its transmission via lymphatic endothelial channels through the host. Several surface receptors act to pass and propagate HIV at the immune synapse, and no current therapy exists to abrogate HIV transmission at this biological complex. We propose an innovative strategy to target a novel ligand-receptor system, Slit/Robo that can block several of the facilitating receptors in the immune synapse. This ligand-receptor pair, we hypothesize, can be uniquely exploited to inhibit HIV passage between cells and HIV spread via lymphatic endothelial channels. We further postulate that this innovative therapeutic approach could be counteracted by cannabinoids, negating its benefit in certain drug abusers. This concern may paradoxically open up a synergistic way to enhance HIV inhibition by Slit/Robo at the immune synapse by additionally blocking relevant cannabinoid receptors. This proposal imagines containing and targeting HIV in restricted anatomic sites and would be a paradigm shift in how HIV/AIDS can be treated.

描述(申请人提供)：最近的研究表明，艾滋病毒感染是在被称为“免疫突触”的免疫细胞复合体中建立的。这些免疫单位有效地将病毒传递给未感染的细胞，并通过淋巴管内皮细胞通道促进其通过宿主传播。几种表面受体在免疫突触传递和传播艾滋病毒，目前还不存在消除艾滋病毒在这一生物复合体中传播的疗法。我们提出了一种创新的策略来靶向一个新的配体-受体系统，Sit/Robo，它可以阻断免疫突触中的几个易化受体。我们假设，这种配体-受体对可以被独特地利用来抑制HIV在细胞之间的传播，以及HIV通过淋巴管内皮通道传播。我们进一步假设，这种创新的治疗方法可能会被大麻类药物抵消，从而否定其对某些吸毒者的好处。这一担忧可能矛盾地开辟了一种协同方式，通过在免疫突触上的Sit/Robo额外阻断相关的大麻素受体来增强对HIV的抑制。这项提议设想在受限的解剖部位控制和靶向艾滋病毒，这将是艾滋病毒/艾滋病治疗方式的一种范式转变。