van Pul Lisa, van Dort Karel A, Girigorie Arginell F, Maurer Irma, Harskamp Agnes M, Kootstra Neeltje A
Amsterdam Institute for Infection and Immunity, Amsterdam, The Netherlands.
Experimental Immunology, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Open Forum Infect Dis. 2024 Aug 5;11(8):ofae434. doi: 10.1093/ofid/ofae434. eCollection 2024 Aug.
Chronic immune activation is one of the hallmarks of human immunodeficiency virus (HIV) pathogenesis. Persistent upregulation of interferons (IFNs) and interferon-stimulated genes (ISGs) has previously been associated with chronic immune activation and HIV progression. Here a longitudinal analysis of the IFN and ISG response during HIV infection was performed to gain insights into the ongoing immune activation during HIV infection.
IFN and ISG levels were determined using quantitative polymerase chain reaction in peripheral blood mononuclear cells of people with HIV at pre-seroconversion, during acute and chronic HIV infection, and during suppressive antiretroviral therapy (ART).
HIV infection induced the expression of a set of 4 ISGs-RSAD2, ISG15, IFI44L, and IFI27-which remained upregulated during chronic infection. This set of ISGs showed no clear correlations with T-cell activation as determined by co-expression of CD38 and HLA-DR. However, a strong correlation with monocyte activation marker soluble CD163 in serum was found. Furthermore, the expression of this ISG cluster was predictive of viral load before ART initiation and, on ART, expression levels normalized to pre-seroconversion levels.
The results presented here suggests that ISG expression is linked to monocyte activation, possibly driven by viral replication.
慢性免疫激活是人类免疫缺陷病毒（HIV）发病机制的标志之一。干扰素（IFN）和干扰素刺激基因（ISG）的持续上调先前已与慢性免疫激活和HIV进展相关。在此进行了一项HIV感染期间IFN和ISG反应的纵向分析，以深入了解HIV感染期间持续的免疫激活情况。
在血清转化前、急性和慢性HIV感染期间以及抑制性抗逆转录病毒治疗（ART）期间，使用定量聚合酶链反应测定HIV感染者外周血单个核细胞中的IFN和ISG水平。
HIV感染诱导了一组4种ISG（RSAD2、ISG15、IFI44L和IFI27）的表达，这些ISG在慢性感染期间持续上调。通过CD38和HLA-DR的共表达确定，这组ISG与T细胞激活无明显相关性。然而，发现其与血清中单核细胞激活标志物可溶性CD163有很强的相关性。此外，该ISG簇的表达可预测ART开始前的病毒载量，并且在ART治疗期间，表达水平恢复到血清转化前的水平。
此处呈现的结果表明，ISG表达与单核细胞激活相关，可能由病毒复制驱动。
