Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors
Transcriptome Sequencing of Peripheral Blood Mononuclear Cells from Elite Controller-Long Term Non Progressors
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DOI：
10.1038/s41598-019-50642-x
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发表时间：
2019-10-03
影响因子：
4.6
通讯作者：
Alcami, Jose
中科院分区：
文献类型：
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作者：
Diez-Fuertes, Francisco;Erick De La Torre-Tarazona, Humberto;Alcami, Jose
精英控制者（EC）-长期非进展者（LTNP）表型代表了在没有治疗的情况下HIV-1控制的自发和有利的模型。通过RNA-Seq对从EC-LTNP收集的外周血单核细胞（PBMC）的转录组进行测序，并与来自疾病进展的其他表型的转录组进行比较。转录丰度估计结合使用监督分类算法允许选择20个基因和假基因，主要涉及干扰素调节的抗病毒机制和转录和翻译的细胞机制，作为疾病进展的最佳预测基因。表型之间的差异表达分析表明，EC-LTNP中钙稳态的改变证明了在钙信号转导级联和细胞内钙动员的几个膜受体的上调，并在这些个体中差异表达的基因的启动子中的NFAT 1/Elk-1结合位点的过度表达。在EC-LTNP中也观察到与HIV-1逆转录和病毒转录相关的宿主基因的协调上调-即p21/CDKN 1A、TNF、IER 3和GADD 45 B。我们还发现，与典型进展者相比，EC-LTNP和病毒血症LTNP中ANKRD 54上调，并且在接受抗逆转录病毒治疗前后，典型进展者中病毒血症导致I型干扰素信号传导明显改变。
The elite controller (EC)-long term non-progressor (LTNP) phenotype represent a spontaneous and advantageous model of HIV-1 control in the absence of therapy. The transcriptome of peripheral blood mononuclear cells (PBMCs) collected from EC-LTNPs was sequenced by RNA-Seq and compared with the transcriptomes from other phenotypes of disease progression. The transcript abundance estimation combined with the use of supervised classification algorithms allowed the selection of 20 genes and pseudogenes, mainly involved in interferon-regulated antiviral mechanisms and cell machineries of transcription and translation, as the best predictive genes of disease progression. Differential expression analyses between phenotypes showed an altered calcium homeostasis in EC-LTNPs evidenced by the upregulation of several membrane receptors implicated in calcium-signaling cascades and intracellular calcium-mobilization and by the overrepresentation of NFAT1/Elk-1-binding sites in the promoters of the genes differentially expressed in these individuals. A coordinated upregulation of host genes associated with HIV-1 reverse transcription and viral transcription was also observed in EC-LTNPs -i.e. p21/CDKN1A, TNF, IER3 and GADD45B. We also found an upregulation of ANKRD54 in EC-LTNPs and viremic LTNPs in comparison with typical progressors and a clear alteration of type-I interferon signaling as a consequence of viremia in typical progressors before and after receiving antiretroviral therapy.