Blimp-1 overexpression is associated with low HIV-1 reservoir and transcription levels in central memory CD4+ T cells from elite controllers
Blimp-1 overexpression is associated with low HIV-1 reservoir and transcription levels in central memory CD4+ T cells from elite controllers
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DOI：
10.1097/qad.0000000000000295
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发表时间：
2014-07-17
期刊：
影响因子：
3.8
通讯作者：
Autran, Brigitte
中科院分区：
文献类型：
--
作者：
de Masson, Adele;Kirilovsky, Amos;Autran, Brigitte
目的：本研究旨在确定在以精英控制者为代表的功能性治愈模型中，艾滋病病毒（HIV）与其宿主之间准平衡的分子机制，这些精英控制者可自发地维持极低水平的HIV储存库。
设计：对感染HIV - 1的精英控制者、病毒血症长期不进展者（vir - LTNPs）以及未感染个体的四种主要静息CD4(+) T细胞亚群进行全基因组转录研究以及细胞相关HIV DNA和HIV RNA水平的定量分析。
方法：我们比较了来自14名感染HIV - 1的个体（包括7名精英控制者（E - LTNPs）和7名病毒血症长期不进展者（vir - LTNPs））以及7名未感染个体的四种主要静息CD4(+) T细胞亚群[初始（T - N）、中央记忆（T - CM）、过渡记忆（T - TM）和效应记忆（T - EM）]的全基因组转录谱（ArrayExpress登录号E - MTAB - 1480）。在每个分选的亚群中同时对HIV - 1细胞DNA和mRNA水平进行定量。
结果：宿主基因转录组遵循亚群分化和病毒血症情况，但在精英控制者中除外，在精英控制者中，作为主要CD4(+)细胞区室的中央记忆T细胞（T - CM）表现出最高的活性，具有三个特定特征，包括T细胞受体和共刺激信号通路的过表达、PRDM - 1/Blimp - 1转录抑制因子的过表达以及I型干扰素相关基因的下调。在各亚群中，PRDM1/Blimp - 1的上调与细胞HIV - DNA和HIV mRNA水平的降低相关。
结论：这种独特的Blimp - 1转录抑制因子特征以及精英控制者的中央记忆T细胞（T - CM）中宿主与病毒转录活性之间的对比表明，Blimp - 1可能参与控制关键的中央记忆T细胞（TCM）亚群中的HIV储存库。（C）2014年威科集团 | 利平科特·威廉姆斯和威尔金斯出版社
Objectives: The aim of the study was to determine the molecular mechanisms underlying the quasi-equilibrium between HIV and its host in the model of functional cure represented by elite controllers who spontaneously maintain exceptionally low levels of HIV reservoirs.Design: Whole-genome transcriptional study and quantification of the cell-associated HIV DNA and HIV RNA levels of the four major resting CD4(+) T-cell subsets in HIV-1-infected elite controllers, viremic long-term nonprogressors (vir-LTNPs), and uninfected individuals.Methods: We compared the whole-genome transcriptional profiles (ArrayExpress accession number E-MTAB-1480) of the four major resting CD4(+) T-cell subsets [naive (T-N), central-memory (T-CM), transitional-memory (T-TM), and effector-memory (T-EM)] from 14 HIV-1-infected individuals including seven elite controllers (E-LTNPs) and seven vir-LTNPs, and from seven uninfected individuals. The HIV-1 cellular DNA and mRNA levels were quantified in parallel in each sorted subset.Results: Host gene transcriptomes followed subset differentiation and viremia except in E-LTNPs wherein T-CM, the main CD4(+) cell compartment, showed the highest activity with three specific signatures involving overexpression of T-cell receptor and costimulation signaling pathways, overexpression of the PRDM-1/Blimp-1 transcriptional repressor, and downmodulation of type-I IFN-related genes. Among subsets, the PRDM1/Blimp-1 upregulation was associated with lower levels of both cellular HIV-DNA and HIV mRNA levels.Conclusion: This unique Blimp-1 transcriptional repressor signature and the contrast between host and virus transcriptional activities in T-CM from elite controllers suggest Blimp-1 might be involved in controlling the HIV reservoirs in the key TCM subset. (C) 2014 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins