Chen Heng-Chang
Center for Population Diagnostics, Lukasiewicz Research Network-PORT Polish Center for Technology Development, 54-066 Wroclaw, Poland.
Vaccines (Basel). 2023 Feb 9;11(2):402. doi: 10.3390/vaccines11020402.
(1) Background: The HIV-1 latent reservoir harboring replication-competent proviruses is the major barrier in the quest for an HIV-1 infection cure. HIV-1 infection at all stages of disease progression is associated with immune activation and dysfunctional production of proinflammatory soluble factors (cytokines and chemokines), and it is expected that during HIV-1 infection, different immune components and immune cells, in turn, participate in immune responses, subsequently activating downstream biological pathways. However, the functional interaction between HIV-1 integration and the activation of host biological pathways is presently not fully understood. (2) Methods: In this work, I used genes targeted by proviruses from published datasets to seek enriched immunologic signatures and host biological pathways alongside HIV-1 infections based on MSigDb and KEGG over-representation analysis. (3) Results: I observed that different combinations of immunologic signatures of immune cell types and proinflammatory soluble factors appeared alongside HIV-1 infections associated with antiretroviral therapy. Moreover, enriched KEGG pathways were often related to "cancer specific types", "immune system", "infectious disease viral", and "signal transduction". (4) Conclusions: The observations in this work suggest that the gene sets harboring provirus integration sites may define specific immune cells and proinflammatory soluble factors during HIV-1 infections associated with antiretroviral therapy.
(1)背景:携带具有复制能力的前病毒的HIV-1潜伏库是寻求治愈HIV-1感染的主要障碍。在疾病进展的所有阶段,HIV-1感染都与免疫激活和促炎可溶性因子(细胞因子和趋化因子)的功能失调产生有关,并且预计在HIV-1感染期间,不同的免疫成分和免疫细胞依次参与免疫反应,随后激活下游生物学途径。然而,目前尚不完全清楚HIV-1整合与宿主生物学途径激活之间的功能相互作用。(2)方法:在这项工作中,我根据MSigDb和KEGG过表达分析,利用已发表数据集中前病毒靶向的基因,寻找与HIV-1感染相关的富集免疫特征和宿主生物学途径。(3)结果:我观察到,与抗逆转录病毒治疗相关的HIV-1感染会出现免疫细胞类型和促炎可溶性因子的不同免疫特征组合。此外,富集的KEGG途径通常与“癌症特定类型”、“免疫系统”、“传染病病毒”和“信号转导”有关。(4)结论:这项工作中的观察结果表明,在前病毒整合位点的基因集可能在与抗逆转录病毒治疗相关的HIV-1感染期间定义特定的免疫细胞和促炎可溶性因子。