HIV-1 activates oxidative phosphorylation in infected CD4 T cells in a human tonsil explant model.
HIV-1 activates oxidative phosphorylation in infected CD4 T cells in a human tonsil explant model.
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DOI：
10.3389/fimmu.2023.1172938
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发表时间：
2023
影响因子：
7.3
通讯作者：
中科院分区：
文献类型：
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作者：
人类免疫缺陷病毒1型（HIV-1）引起慢性、不可治愈的感染，导致HIV-1（PWH）患者的免疫激活和慢性炎症，即使抗逆转录病毒治疗（ART）进行病毒学抑制。淋巴结构作为病毒潜伏和免疫激活的储库的作用与慢性炎症机制有关。尽管如此，在淋巴组织内的不同细胞类型中由HIV-1感染诱导的特异性转录组学变化仍然未被探索。在这项研究中，我们利用人类扁桃体外植体从健康的人供体和感染他们与HIV-1离体。我们进行了单细胞RNA测序（scRNA-seq）来分析组织中代表的细胞类型，并研究感染对基因表达谱和炎症信号通路的影响。我们的分析表明，感染的CD 4 + T细胞表现出与氧化磷酸化相关的基因上调。此外，暴露于病毒但未感染的巨噬细胞显示与NLRP 3炎性体途径相关的基因表达增加。这些发现提供了有价值的见解特定的转录组的变化引起的HIV-1感染在淋巴组织内的不同类型的细胞。感染的CD 4 + T细胞中氧化磷酸化的激活和巨噬细胞中的促炎反应可能有助于在PWH中观察到的慢性炎症，尽管ART。了解这些机制对于制定有针对性的治疗策略以根除PWH中的HIV-1感染至关重要。
Human immunodeficiency virus type 1 (HIV-1) causes a chronic, incurable infection leading to immune activation and chronic inflammation in people with HIV-1 (PWH), even with virologic suppression on antiretroviral therapy (ART). The role of lymphoid structures as reservoirs for viral latency and immune activation has been implicated in chronic inflammation mechanisms. Still, the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue remain unexplored. In this study, we utilized human tonsil explants from healthy human donors and infected them with HIV-1 ex vivo. We performed single-cell RNA sequencing (scRNA-seq) to analyze the cell types represented in the tissue and to investigate the impact of infection on gene expression profiles and inflammatory signaling pathways. Our analysis revealed that infected CD4+ T cells exhibited upregulation of genes associated with oxidative phosphorylation. Furthermore, macrophages exposed to the virus but uninfected showed increased expression of genes associated with the NLRP3 inflammasome pathway. These findings provide valuable insights into the specific transcriptomic changes induced by HIV-1 infection in different cell types within lymphoid tissue. The activation of oxidative phosphorylation in infected CD4+ T cells and the proinflammatory response in macrophages may contribute to the chronic inflammation observed in PWH despite ART. Understanding these mechanisms is crucial for developing targeted therapeutic strategies to eradicate HIV-1 infection in PWH.
基于整合酶抑制剂的ART对未经艾滋病毒的艾滋病患者的NLRP3炎症体的影响。
影响因子：
4.2
作者：
Toribio M;Burdo TH;Fulda ES;Cetlin M;Chu SM;Feldpausch MN;Robbins GK;Neilan TG;Melbourne K;Grinspoon SK;Zanni MV
通讯作者：
Zanni MV