Reanalysis of Gene Expression Profiles of CD4+ T Cells Treated with HIV-1 Latency Reversal Agents.
Reanalysis of Gene Expression Profiles of CD4+ T Cells Treated with HIV-1 Latency Reversal Agents.
复制标题
重新分析接受 HIV-1 潜伏期逆转剂治疗的 CD4+ T 细胞的基因表达谱。
DOI：
10.3390/microorganisms8101505
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发表时间：
2020-09-30
期刊：
影响因子：
4.5
通讯作者：
Crovella S
中科院分区：
文献类型：
--
作者：
Campos Coelho AV;Moura RR;Crovella S
人类免疫缺陷病毒(HIV-1)会导致CD4+T细胞逐渐耗尽，从而阻碍免疫功能。目前对抗病毒的实验策略主要集中在通过寻找潜伏期反转剂(LRA)来重新激活病毒库中的潜伏HIV-1，使免疫系统能够检测到病毒。我们假设，如果已知LRA的存在所引发的共同分子途径，或许可以找到新的、更有效的“休克和杀死”策略。因此，本研究的目的是通过转录组分析重新评估RNA-Seq分析，以寻找潜伏期逆转过程中的差异表达基因(DEG)。我们通过在基因表达总览(GEO)和PubMed数据库中的系统搜索，选择了6项研究(总共45个样本：16个阴性对照和29个经LRA处理的CD4+T细胞)和11个LRA策略。对原始读数进行了修剪、计数和标准化。接下来，我们在这些独立的实验中检测到了一致的DEG。AZD5582、罗米迪辛和亚苯基异羟肟酸(SAHA)是调节大多数基因的LRA。我们检测到这三个LRA共有948个DEG。基因本体论分析和与其他文献来源的交叉参考表明，细胞的激活、分化和信号转导丰富，特别是丝裂原活化蛋白激酶(MAPK)和Rho-GTP酶途径。
The human immunodeficiency virus (HIV-1) causes a progressive depletion of CD4+ T cells, hampering immune function. Current experimental strategies to fight the virus focus on the reactivation of latent HIV-1 in the viral reservoir to make the virus detectable by the immune system, by searching for latency reversal agents (LRAs). We hypothesize that if common molecular pathways elicited by the presence of LRAs are known, perhaps new, more efficient, “shock-and-kill” strategies can be found. Thus, the objective of the present study is to re-evaluate RNA-Seq assays to find differentially expressed genes (DEGs) during latency reversal via transcriptome analysis. We selected six studies (45 samples altogether: 16 negative controls and 29 LRA-treated CD4+ T cells) and 11 LRA strategies through a systematic search in Gene Expression Omnibus (GEO) and PubMed databases. The raw reads were trimmed, counted, and normalized. Next, we detected consistent DEGs in these independent experiments. AZD5582, romidepsin, and suberanilohydroxamic acid (SAHA) were the LRAs that modulated most genes. We detected 948 DEGs shared by those three LRAs. Gene ontology analysis and cross-referencing with other sources of the literature showed enrichment of cell activation, differentiation and signaling, especially mitogen-activated protein kinase (MAPK) and Rho-GTPases pathways.
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影响因子：
8.8
作者：
Bosque A;Nilson KA;Macedo AB;Spivak AM;Archin NM;Van Wagoner RM;Martins LJ;Novis CL;Szaniawski MA;Ireland CM;Margolis DM;Price DH;Planelles V
通讯作者：
Planelles V
DOI：
10.1016/s2352-3018(20)30069-2
发表时间：
2020-05
期刊：
The lancet. HIV
影响因子：
--
作者：
Gupta RK;Peppa D;Hill AL;Gálvez C;Salgado M;Pace M;McCoy LE;Griffith SA;Thornhill J;Alrubayyi A;Huyveneers LEP;Nastouli E;Grant P;Edwards SG;Innes AJ;Frater J;Nijhuis M;Wensing AMJ;Martinez-Picado J;Olavarria E
通讯作者：
Olavarria E
影响因子：
56.9
作者：
BARRESINOUSSI, F;CHERMANN, JC;MONTAGNIER, L
通讯作者：
MONTAGNIER, L
影响因子：
6.2
作者：
Henderson, Lisa J.;Al-Harthi, Lena
通讯作者：
Al-Harthi, Lena
影响因子：
3.7
作者：
Costa-Silva J;Domingues D;Lopes FM
通讯作者：
Lopes FM