Human Immunodeficiency Virus-Induced Interferon-Stimulated Gene Expression Is Associated With Monocyte Activation and Predicts Viral Load.

IF 3.8 4区医学 Q2 IMMUNOLOGY Open Forum Infectious Diseases Pub Date : 2024-08-05 eCollection Date: 2024-08-01 DOI:10.1093/ofid/ofae434

Lisa van Pul, Karel A van Dort, Arginell F Girigorie, Irma Maurer, Agnes M Harskamp, Neeltje A Kootstra

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Abstract

Background: 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.

Methods: 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).

Results: 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.

Conclusions: The results presented here suggests that ISG expression is linked to monocyte activation, possibly driven by viral replication.

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人类免疫缺陷病毒诱导的干扰素刺激基因表达与单核细胞活化有关，并可预测病毒载量。

背景：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（IFNs）和干扰素刺激基因（ISGs）的持续上调曾被认为与慢性免疫激活和艾滋病进展有关。在此，我们对 HIV 感染期间的 IFN 和 ISG 反应进行了纵向分析，以深入了解 HIV 感染期间持续的免疫激活：方法：使用定量聚合酶链反应测定血清转换前、急性和慢性 HIV 感染期间以及抑制性抗逆转录病毒疗法（ART）期间 HIV 感染者外周血单核细胞中的 IFN 和 ISG 水平：结果：HIV 感染会诱导一组 4 个 ISGs-RSAD2、ISG15、IFI44L 和 IFI27 的表达，这些 ISGs 在慢性感染期间仍会上调。这组 ISGs 与 CD38 和 HLA-DR 的共同表达所确定的 T 细胞活化没有明显的相关性。然而，研究人员发现这组 ISG 与血清中的单核细胞活化标志物可溶性 CD163 有很强的相关性。此外，在开始抗逆转录病毒疗法之前，该 ISG 簇的表达可预测病毒载量，而在开始抗逆转录病毒疗法后，其表达水平将恢复到血清转换前的正常水平：本文的研究结果表明，ISG 的表达与单核细胞活化有关，可能是由病毒复制驱动的。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Open Forum Infectious Diseases Medicine-Neurology (clinical)

CiteScore

6.70

自引率

4.80%

发文量

630

审稿时长

9 weeks

期刊介绍： Open Forum Infectious Diseases provides a global forum for the publication of clinical, translational, and basic research findings in a fully open access, online journal environment. The journal reflects the broad diversity of the field of infectious diseases, and focuses on the intersection of biomedical science and clinical practice, with a particular emphasis on knowledge that holds the potential to improve patient care in populations around the world. Fully peer-reviewed, OFID supports the international community of infectious diseases experts by providing a venue for articles that further the understanding of all aspects of infectious diseases.