Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals
Gene expression profile of HIV-1 Tat expressing cells: a close interplay between proliferative and differentiation signals
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DOI：
10.1186/1472-2091-3-14
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发表时间：
2002-01-01
期刊：
影响因子：
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通讯作者：
Kashanchi, Fatah
中科院分区：
文献类型：
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作者：
de la Fuente, Cynthia;Santiago, Francisco;Kashanchi, Fatah
背景：表达谱为快速宿主基因组功能分析提供了很大的希望。感染中的宿主表达谱可以作为病毒感染细胞的普遍表型，这是合理的。在这里，我们描述了最关键的病毒激活剂之一，TAT，在HIV-1感染和表达TAT的细胞中的作用。我们利用来自未感染的HIV-1潜伏感染细胞以及表达TAT的细胞的微阵列分析来破译与该病毒激活剂相关的一些细胞变化。结果：利用未感染的HIV-1潜伏感染细胞和表达TAT的细胞，我们观察到在表达TAT的细胞中大多数细胞宿主基因下调。在表达TAT的细胞中，具有内在受体酪氨酸激酶(RTK)活性的细胞受体和介导RTK功能的信号转导成员，包括Ras-Raf-MEK通路，下调最为明显。调节激素受体相关基因表达的转录辅助激活因子，如p300/CBP和SRC-1，也被发现下调。下调受体可能会使潜伏的HIV-1感染细胞要么躲避免疫系统，要么避免细胞外分化信号。一些上调的基因包括HIV-1进入的辅助受体、翻译机制和细胞周期调节蛋白。结论：我们通过微阵列方法证明了HIV-1 Tat能够调控许多参与细胞信号转译的细胞基因，最终控制宿主的增殖和分化信号。
Background: Expression profiling holds great promise for rapid host genome functional analysis. It is plausible that host expression profiling in an infection could serve as a universal phenotype in virally infected cells. Here, we describe the effect of one of the most critical viral activators, Tat, in HIV-1 infected and Tat expressing cells. We utilized microarray analysis from uninfected, latently HIV-1 infected cells, as well as cells that express Tat, to decipher some of the cellular changes associated with this viral activator.Results: Utilizing uninfected, HIV-1 latently infected cells, and Tat expressing cells, we observed that most of the cellular host genes in Tat expressing cells were down-regulated. The down-regulation in Tat expressing cells is most apparent on cellular receptors that have intrinsic receptor tyrosine kinase (RTK) activity and signal transduction members that mediate RTK function, including Ras-Raf-MEK pathway. Co-activators of transcription, such as p300/CBP and SRC-1, which mediate gene expression related to hormone receptor genes, were also found to be down-regulated. Down-regulation of receptors may allow latent HIV-1 infected cells to either hide from the immune system or avoid extracellular differentiation signals. Some of the genes that were up-regulated included co-receptors for HIV-1 entry, translation machinery, and cell cycle regulatory proteins.Conclusions: We have demonstrated, through a microarray approach, that HIV-1 Tat is able to regulate many cellular genes that are involved in cell signaling, translation and ultimately control the host proliferative and differentiation signals.