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: 8116997
• 负责人: JEROME E GROOPMAN
• 金额: $ 81.63万
• 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/8116997
• 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（由申请人提供）：最近的研究表明，HIV感染是在称为“免疫突触”的免疫细胞复合物中建立的。“这些免疫单位有效地将病毒传递到未感染的细胞，并促进其通过淋巴内皮通道通过宿主的传播。几种表面受体在免疫突触处传递和传播HIV，目前还没有治疗方法可以消除HIV在这个生物复合体中的传播。我们提出了一种创新的策略，以靶向一种新的配体-受体系统，Slit/Robo，它可以阻断免疫突触中的几种促进受体。我们假设，这种配体-受体对可以被独特地利用来抑制HIV在细胞之间的通过和HIV通过淋巴管内皮通道的传播。我们进一步假设，这种创新的治疗方法可能会被大麻素抵消，从而否定其对某些药物滥用者的益处。这种担忧可能矛盾地开辟了一种协同方式，通过额外阻断相关的大麻素受体来增强Slit/Robo在免疫突触处的HIV抑制作用。这项提案设想在有限的解剖部位遏制和靶向艾滋病毒，这将是艾滋病毒/艾滋病治疗方式的一个范式转变。