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艾滋病毒感染患者抗逆转录病毒治疗后免疫应答调节的早期转录组特征

Ekaterina A Stolbova¹, Anastasia V Pokrovskaya^2,3, Andrey B Shemshura⁴

¹Laboratory of Big Data Analysis for Digital Pharmacology, Department of Bioinformatics, Institute of Biomedical Chemistry, Pogodinskaya Street 10-8, 119121 Moscow, Russia.

International journal of molecular sciences

|November 13, 2025

概括

人类免疫缺陷病毒 (HIV) 的抗逆转录病毒疗法 (ART) 抑制病毒复制. 早期免疫恢复涉及降低干扰素信号和恢复T细胞功能,重新平衡抗病毒环境.

科学领域:

免疫学免疫学免疫学
病毒学病毒学
基因组学就是基因组学.

背景情况:

人类免疫缺陷病毒 (HIV) 是一个严重的全球健康问题.
抗逆转录病毒疗法 (ART) 通过抑制病毒载量和帮助免疫恢复,对控制艾滋病毒至关重要.
在ART启动后免疫基因表达的早期分子变化尚未完全理解.

研究的目的:

在HIV感染个体中启动组合ART后,研究免疫相关的转录变化的早期分子机制.
在ART的24周内对外围血液单核细胞 (PBMC) 的转录基因变异进行表征.

主要方法:

大量RNA测序在8名先前未接受ART治疗的男性患者的PBMC上进行,在24周的联合ART (TDF,3TC,DTG) 治疗之前和之后进行.
使用了差异基因表达分析 (DESeq2),基因组丰富分析 (GSEA),主要成分分析 (PCA),层次聚类和蛋白质-蛋白质相互作用 (PPI) 网络分析.
确定了参与免疫反应和转录调节的关键基因和途径.

主要成果:

鉴定了87个差异表达的基因,其中67个是干扰素刺激的基因 (例如IFI44L,ISG15,STAT1) 和20个是上调的转录,主要是核糖体蛋白质伪基因.
功能丰富分析表明ART后的I型干扰素和其他抗病毒信号通路的抑制.
在ART治疗24周后,PCA和等级聚类显示了PBMCs的明显转录转移.

结论:

艾滋病毒患者在ART启动后的早期免疫恢复的特点是慢性干扰素驱动的免疫激活的下调.
这种转录转移表明T细胞功能能力的部分恢复和抗病毒免疫环境的再平衡.
这些发现为早期艾滋病毒治疗期间免疫复原的分子动力学提供了洞察力.

关键词:

艾滋病病毒艾滋病病毒艾滋病病毒在 RNA 序列中,RNA 序列抗逆转录病毒药物治疗基因表达的基因表达方式配对分析对对分析.

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