Ma Jinmin, Zhao Fang, Su Wei, Li Qiongfang, Li Jiandong, Ji Jingkai, Deng Yong, Zhou Yang, Wang Xinfa, Yang Huanming, Saksena Nitin K, Kristiansen Karsten, Wang Hui, Liu Yingxia
BGI-Shenzhen, Shenzhen 518083, PR China.
Laboratory of Genomics and Molecular Biomedicine, Department of Biology, University of Copenhagen, Copenhagen 2100, Denmark.
Per Med. 2018 Jul 1;15(4):251-269. doi: 10.2217/pme-2017-0084. Epub 2018 Jul 9.
Co-infection in HIV-1 patients with Mycobacterium tuberculosis poses considerable risk of developing the immune reconstitution inflammatory syndrome (IRIS), especially upon the initiation of antiretroviral therapy (ART). Methodology & results: For transcriptomic analysis, peripheral blood mononuclear cells' whole gene expression was used from three patient groups: HIV (H), HIV-TB (HT), HIV-TB with IRIS (HTI). Pathway enrichment and functional analysis was performed before and after highly active ART. Genes in the interferon-stimulating and ZNF families maintained tight functional interaction and tilted the balance in favor of TB-IRIS.
DISCUSSION & CONCLUSION: The functional impairment of interaction between ZNF genes and interferon-stimulated genes, along with higher expression of S100A8/S100A9 genes possibly forms the genomic basis of TB-IRIS in a subset of HIV patients while on highly active ART.
HIV-1患者合并结核分枝杆菌感染有发生免疫重建炎症综合征(IRIS)的重大风险,尤其是在开始抗逆转录病毒治疗(ART)时。方法与结果:为进行转录组分析,使用了三个患者组外周血单个核细胞的全基因表达:HIV组(H)、HIV-结核组(HT)、伴有IRIS的HIV-结核组(HTI)。在高效ART前后进行了通路富集和功能分析。干扰素刺激基因家族和锌指蛋白(ZNF)家族中的基因保持紧密的功能相互作用,并使平衡向有利于结核-IRIS的方向倾斜。
ZNF基因与干扰素刺激基因之间相互作用的功能受损,以及S100A8/S100A9基因的较高表达,可能在一部分接受高效ART的HIV患者中构成结核-IRIS的基因组基础。