Exploiting Natural Killer cells in HIV/HBV co-infection to achieve eradication

利用适应性NK细胞在HIV/HBV混合感染中的根除作用 项目摘要/摘要 尽管联合抗逆转录病毒治疗(ART)和抗艾滋病毒双重活性的好处 和乙肝病毒，HIV/乙肝病毒混合感染和乙肝病毒单独感染的结局的差异 人口仍然存在。我们目前对免疫恢复程度的认识 在这两组人的治疗下，特别是在肝脏免疫反应方面， 找出显著的知识差距和发展有效功能的障碍 治愈。最近的技术进步，包括使用单细胞RNA测序(scRNA- 和高通量单细胞分析，以及细针抽吸物(FNAs) 来自适当配对的临床队列的肝脏提供了新的令人兴奋的探索机会 肝脏免疫信号与外周免疫信号。这些创新的方法将应用于 确定免疫细胞的转录图谱、蛋白质组学和功能特征 人类免疫缺陷病毒/乙肝病毒混合感染与单一乙肝病毒感染之间的肝脏和外周血中的种群 在一个全新的水平上解决感染患者。我们将特别强调 具有适应性的自然杀伤(NK)细胞和独特的NK细胞亚群 “记忆”的特征丰富在肝脏中。这些专门化的亚群出现在 对慢性病毒感染的反应和使用HIV编码的信封接种疫苗 具有增强功能的蛋白质和具有巨大潜力的有效 控制病毒复制。因此，适应性NK细胞的临床开发代表着一种 加强慢性病毒感染治疗的变革性方法。我们的目标是开发一种 用于扩展适应性NK细胞的强大且可扩展的平台 功能性和可预测的选择性，可以绕过许多固有的限制 到目前为止测试的各种免疫治疗方法，代表了一种新的途径 新的或补充的治疗策略。

Exploiting adaptive NK cells in HIV/HBV co-infection towards eradication Project Summary/Abstract Despite the benefits of combined antiretroviral treatment (ART) with dual activity against HIV and HBV, the differences in outcome between HIV/HBV co-infected and HBV mono-infected populations still persist. Our current understanding of the degree of immunological recovery with therapy in these two groups, in particular in terms of hepatic immune responses is scarce, identifying a significant knowledge gap and a barrier to the development of effective functional cures. Recent technical advances, including the use of single-cell RNA sequencing (scRNA- seq) and high-throughput single cell analysis along with fine needle aspirates (FNAs) of the liver from appropriately matched clinical cohorts provide new exciting opportunities to probe hepatic versus peripheral immune signatures. These innovative approaches will be applied to ascertain the transcriptional landscape, proteomic and functional features of immune cell populations in the liver and peripheral blood between HIV/HBV co-infected versus HBV mono- infected patients at an entirely new level of resolution. Particular emphasis will be placed on Natural Killer (NK) cells with adaptive properties and unique subpopulations of NK cells with ‘memory’ features enriched in the liver. These specialised subpopulations that arise in response to chronic viral infections and following vaccination with HIV-encoded envelope protein and endowed with enhanced functionality hold tremendous potential for effective control of virus replication. Therefore, clinical exploitation of adaptive NK cells represents a transformative approach to augment therapy of chronic viral infection. We aim to develop a robust and scalable platform for the expansion of adaptive NK cells with enhanced functionality and predictable selectivity that could circumvent many of the limitations inherent to the various immunotherapeutic approaches tested so far, representing a novel avenue for new or complementary curative strategies.