A proteomic glimpse into the initial global epigenetic changes during HIV infection.
A proteomic glimpse into the initial global epigenetic changes during HIV infection.
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DOI：
10.1002/pmic.201400116
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发表时间：
2014-10
期刊：
影响因子：
3.4
通讯作者：
Garcia, Benjamin A.
中科院分区：
文献类型：
--
作者：
Britton, Laura-Mae P.;Sova, Pavel;Belisle, Sarah;Liu, Shichong;Chan, Eric Y.;Katze, Michael G.;Garcia, Benjamin A.
HIV-1复制需要将病毒DNA插入宿主基因组，这是由HIV-1整合酶催化的。这种整合事件可以导致染色质景观和基因转录的巨大变化。在这项研究中，我们试图将组蛋白翻译后修饰(PTM)丰度的广泛变化与宿主转录活性的同样动态变化联系起来。为了完全捕捉HIV感染过程中发生的变化，我们从HIV感染、紫外线灭活的HIV感染和模拟感染的SUP-T1细胞中提取了组蛋白和mRNA。然后，我们利用NanoLC-MS/MS分析了组蛋白PTM谱的变化，以及组蛋白脱乙酰酶、乙酰转移酶、去甲基酶、甲基转移酶和组蛋白伴侣蛋白等染色质相关酶的表达。正如预期的那样，我们观察到组蛋白PTM丰度的重大变化，我们将其与相关染色质酶的mRNA表达的巨大波动联系在一起。然而，我们发现HIV和HIVUV(紫外线灭活)感染之间的差异很小，这表明HIV感染过程中组蛋白PTM的最初变化来自宿主对感染的反应，而不是由于HIV病毒操纵转录机制。我们相信，这些初步实验可以为未来对组蛋白PTM调控的HIV复制周期进展方面的靶向操纵提供基础。
HIV-1 replication requires the insertion of viral DNA into the host genome, which is catalyzed by HIV-1 integrase. This integration event can lead to vast changes in the chromatin landscape and gene transcription. In this study, we sought to correlate the extensive changes of histone post-translation modification (PTM) abundances with the equally dynamic shifts in host transcriptional activity. To fully capture the changes that were occurring during the course of HIV-infection, we performed time-courses in which we extracted both histones and mRNA from HIV-infected, UV-inactivated HIV-infected and mock-infected SUP-T1 cells. We then analyzed the alterations to histone PTM profiles using nanoLC-MS/MS, as well as the expression of chromatin-associated enzymes, such as histone deacetylases, acetyltransferases, demethylases, methyltransferases and histone chaperone proteins. As expected, we observed major changes in histone PTM abundances, which we linked to massive fluctuations in mRNA expression of associated chromatin enzymes. However, we find few differences between HIV and HIVUV (UV-inactivated) infection, which suggests that initial histone PTM changes during HIV infection are from the host in response to the infection, and not due to the HIV virus manipulating the transcriptional machinery. We believe that these preliminary experiments can provide a basis for future forays into targeted manipulations of histone PTM-regulated aspects of HIV progression through its replication cycle.
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