Microarray study reveals that HIV-1 induces rapid type-I interferon-dependent p53 mRNA up-regulation in human primary CD4+ T cells.
Microarray study reveals that HIV-1 induces rapid type-I interferon-dependent p53 mRNA up-regulation in human primary CD4+ T cells.
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DOI：
10.1186/1742-4690-6-5
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发表时间：
2009-01-15
期刊：
影响因子：
3.3
通讯作者：
Tremblay, Michel J.
中科院分区：
文献类型：
--
作者：
Imbeault, Michael;Ouellet, Michel;Tremblay, Michel J.
感染HIV-1已被证明会改变大量宿主细胞基因的表达。然而，以前的研究，目的是调查推定的HIV-1诱导的宿主基因表达的调制大多已在建立的人类细胞系。为了更好地接近自然条件，我们使用来自Affytelum的商业寡核苷酸微阵列监测了暴露于HIV-1的人原代CD 4 + T淋巴细胞高度富集的细胞群中的基因表达变化。我们在这里报告，HIV-1影响许多重要的生物学过程，如DNA修复，细胞周期，RNA代谢和细胞凋亡相关基因的表达。值得注意的是，p53肿瘤抑制基因和参与p53稳态的基因（如GADD 34）的表达在mRNA水平上被HIV-1上调。这一观察结果与先前报道的在蛋白水平上的p53磷酸化和稳定化不同，后者先于HIV-1诱导的细胞凋亡。我们提出的证据表明，HIV-1介导的p53基因表达的增加与病毒介导的I型干扰素（即IFN-α和IFN-β）的诱导有关。这些观察结果对我们理解HIV-1的发病机制具有重要意义，特别是在病毒诱导的CD 4 + T细胞耗竭方面。
Infection with HIV-1 has been shown to alter expression of a large array of host cell genes. However, previous studies aimed at investigating the putative HIV-1-induced modulation of host gene expression have been mostly performed in established human cell lines. To better approximate natural conditions, we monitored gene expression changes in a cell population highly enriched in human primary CD4+ T lymphocytes exposed to HIV-1 using commercial oligonucleotide microarrays from Affymetrix. We report here that HIV-1 influences expression of genes related to many important biological processes such as DNA repair, cellular cycle, RNA metabolism and apoptosis. Notably, expression of the p53 tumor suppressor and genes involved in p53 homeostasis such as GADD34 were up-regulated by HIV-1 at the mRNA level. This observation is distinct from the previously reported p53 phosphorylation and stabilization at the protein level, which precedes HIV-1-induced apoptosis. We present evidence that the HIV-1-mediated increase in p53 gene expression is associated with virus-mediated induction of type-I interferon (i.e. IFN-α and IFN-β). These observations have important implications for our understanding of HIV-1 pathogenesis, particularly in respect to the virus-induced depletion of CD4+ T cells.
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