慢性HIV感染个体外周血单个核细胞的整体转录组特征。

IF 3.4 2区生物学 Q2 BIOTECHNOLOGY & APPLIED MICROBIOLOGY

Genomics Pub Date : 2025-07-08 DOI:10.1016/j.ygeno.2025.111082

Han-Ying Wang , Xi Wang , Qian-Qian Zhang , Xing-Zhong Miao , Liang-Juan Chen , Li-Jun Sun , Hong-Bo Shi

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引用次数: 0

摘要

背景：获得性免疫缺陷综合征（AIDS）是由人类免疫缺陷病毒（HIV）感染引起的，是世界范围内最严重的传染病之一。目前的预防和控制状况仍然至关重要。最近的研究越来越强调细胞代谢在调节免疫反应和控制感染中的重要作用。然而，在感染HIV的不同人群中是否存在不同的免疫代谢谱仍有待研究。在这项研究中，我们采用RNA-seq技术来探索不同HIV感染免疫代谢的差异特征。方法：为了研究HIV感染者外周血单个核细胞（PBMCs）的代谢差异，我们采集了18例HIV感染者的外周血单个核细胞（PBMCs）。该队列包括4名免疫应答者（IRs）， 5名免疫无应答者（INRs）， 5名维持高病毒载量的典型进展者（TPs）和4名精英控制者（ECs），他们在未经治疗的情况下维持低水平的病毒复制。我们对来自这些患者的pbmc进行了单细胞测序，并比较了IRs和INRs以及ec和tp的结果。结果：我们的研究结果显示，与IRs相比，INRs中存在显著的代谢失调和炎症状态改变。这些改变主要在嘌呤代谢、氧化磷酸化（OXPHOS）和糖酵解途径中观察到，以及氨基酸和脂肪酸代谢途径的改变。此外，我们还发现了以GNLY高表达为特征的CD8+ t细胞群亚群中的变异，GNLY主要发挥细胞毒性作用。ECs和TPs之间的代谢途径也存在差异；然而，这些变化主要集中在OXPHOS和戊糖磷酸途径，而糖酵解途径无显著差异。

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Global transcriptome characterization of peripheral blood mononuclear cells in individuals with chronic HIV infection

Background

Acquired Immune Deficiency Syndrome (AIDS), resulting from Human Immunodeficiency Virus (HIV) infection, is one of the most severe infectious diseases worldwide. The current state of prevention and control remains critical. Recent studies have increasingly highlighted the significant role of cellular metabolism in regulating immune responses and managing infections. However, whether distinct immunometabolic profiles exist among different groups infected with HIV remains to be investigated. In this study, we employed RNA-seq technology to explore the differential characterization of immune metabolism across various HIV infections.

Methods

To investigate the metabolic differences in peripheral blood mononuclear cells (PBMCs) from HIV-infected populations, we obtained PBMCs from 18 individuals diagnosed with HIV. This cohort included four Immune Responders (IRs), five Immune Non-Responders (INRs), five typical progressors (TPs) who maintained high viral loads, and four Elite Controllers (ECs) who sustained low levels of viral replication without treatment. We conducted single-cell sequencing on the PBMCs derived from these patients and compared the results between IRs and INRs, as well as ECs and TPs.

Results

Our findings revealed significant metabolic dysregulation and altered inflammatory states in INRs compared to IRs. These alterations were primarily observed in purine metabolism, oxidative phosphorylation (OXPHOS) and glycolysis pathways, as well as modifications in amino acid and fatty acid metabolism pathways. Furthermore, we identified variations within a subset of CD8⁺ T-cell populations characterized by high expression of GNLY, which predominantly exerts cytotoxic effects. Differences in metabolic pathways were also noted between ECs and TPs; however, these changes mainly focused on OXPHOS and pentose phosphate pathways while no significant differences were observed in glycolysis pathway.

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来源期刊

Genomics 生物-生物工程与应用微生物

CiteScore

9.60

自引率

2.30%

发文量

260

审稿时长

60 days

期刊介绍： Genomics is a forum for describing the development of genome-scale technologies and their application to all areas of biological investigation. As a journal that has evolved with the field that carries its name, Genomics focuses on the development and application of cutting-edge methods, addressing fundamental questions with potential interest to a wide audience. Our aim is to publish the highest quality research and to provide authors with rapid, fair and accurate review and publication of manuscripts falling within our scope.