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首页> 外文期刊>BMC Medical Genomics >Genome-wide search for the genes accountable for the induced resistance to HIV-1 infection in activated CD4+ T cells: apparent transcriptional signatures, co-expression networks and possible cellular processes
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Genome-wide search for the genes accountable for the induced resistance to HIV-1 infection in activated CD4+ T cells: apparent transcriptional signatures, co-expression networks and possible cellular processes

机译：全基因组搜索寻找激活的CD4 + T细胞中对HIV-1感染的诱导抗性的基因：明显的转录特征，共表达网络和可能的细胞过程

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Background Upon co-stimulation with CD3/CD28 antibodies, activated CD4?+?T cells were found to lose their susceptibility to HIV-1 infection, exhibiting an induced resistant phenotype. This rather unexpected phenomenon has been repeatedly confirmed but the underlying cell and molecular mechanisms are still unknown. Methods We first replicated the reported system using the specified Dynal beads with PHA/IL-2-stimulated and un-stimulated cells as controls. Genome-wide expression and analysis were then performed by using Agilent whole genome microarrays and established bioinformatics tools. Results We showed that following CD3/CD28 co-stimulation, a homogeneous population emerged with uniform expression of activation markers CD25 and CD69 as well as a memory marker CD45RO at high levels. These cells differentially expressed 7,824 genes when compared with the controls on microarrays. Series-Cluster analysis identified 6 distinct expression profiles containing 1,345 genes as the representative signatures in the permissive and resistant cells. Of them, 245 (101 potentially permissive and 144 potentially resistant) were significant in gene ontology categories related to immune response, cell adhesion and metabolism. Co-expression networks analysis identified 137 “key regulatory” genes (84 potentially permissive and 53 potentially resistant), holding hub positions in the gene interactions. By mapping these genes on KEGG pathways, the predominance of actin cytoskeleton functions, proteasomes, and cell cycle arrest in induced resistance emerged. We also revealed an entire set of previously unreported novel genes for further mining and functional validation. Conclusions This initial microarray study will stimulate renewed interest in exploring this system and open new avenues for research into HIV-1 susceptibility and its reversal in target cells, serving as a foundation for the development of novel therapeutic and clinical treatments.
机译：背景技术在与CD3 / CD28抗体共同刺激下，发现活化的CD4β+ΔT细胞失去了对HIV-1感染的敏感性，表现出诱导的耐药表型。这种相当出乎意料的现象已经被反复证实，但是潜在的细胞和分子机制仍然未知。方法我们首先使用指定的Dynal珠与PHA / IL-2刺激和未刺激的细胞作为对照，复制了报道的系统。然后使用安捷伦全基因组微阵列和已建立的生物信息学工具进行全基因组表达和分析。结果我们显示，在CD3 / CD28共同刺激后，出现了均一的群体，其均以高水平的活化标记CD25和CD69以及记忆标记CD45RO均匀表达。与微阵列上的对照相比，这些细胞差异表达了7,824个基因。 Series-Cluster分析确定了6个不同的表达谱，其中包含1,345个基因作为许可细胞和耐药细胞中的代表性标记。其中有245个（101个可能允许和144个可能耐药）在与免疫反应，细胞粘附和代谢有关的基因本体论类别中很重要。共表达网络分析确定了137个“关键调控”基因（84个可能允许的基因和5​​3个可能耐药的基因），它们在基因相互作用中占据中心位置。通过将这些基因定位在KEGG途径上，出现了肌动蛋白细胞骨架功能，蛋白酶体和细胞周期停滞在诱导抗性中的优势。我们还揭示了一整套先前未报道的新基因，用于进一步挖掘和功能验证。结论最初的微阵列研究将激发人们对探索该系统的新兴趣，并为研究HIV-1敏感性及其在靶细胞中的逆转开辟新的途径，为开发新型治疗和临床疗法奠定基础。

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