Quantitative analysis of human immunodeficiency virus type 1-infected CD4+ cell proteome:: Dysregulated cell cycle progression and nuclear transport coincide with robust virus production
Quantitative analysis of human immunodeficiency virus type 1-infected CD4+ cell proteome:: Dysregulated cell cycle progression and nuclear transport coincide with robust virus production
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DOI：
10.1128/jvi.00288-07
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发表时间：
2007-07-01
影响因子：
5.4
通讯作者：
Katze, Michael G.
中科院分区：
文献类型：
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作者：
Chan, Eric Y.;Qian, Wei-Jun;Katze, Michael G.
在功能基因组水平上对人类免疫缺陷病毒1型（HIV-1）感染的全球宿主反应知之甚少。包括我们自己在内的几个实验室的微阵列分析表明，HIV-1感染导致宿主mRNA丰度和几种细胞生物学途径的调节发生显著变化。然而，目前还不清楚这些变化在蛋白质水平上会带来什么后果。在这里，我们报告了感染人类免疫缺陷病毒I型（HIV-1）的LAI株后CD 4 + CEMx 174细胞系中类似于3，200种蛋白质的表达水平;使用液相色谱-质谱联用技术评估了这些蛋白质稳定同位素标记和准确的质量和时间标签方法。此外，我们发现，687（21%）的蛋白质在感染后36 h的病毒生产高峰时发生了大量变化。途径分析表明，蛋白质的差异表达集中在选择的生物途径，例如泛素化的泛素结合酶，核质转运的载体蛋白，细胞周期进程中的细胞周期蛋白依赖性激酶，和柠檬酸循环途径的丙酮酸脱氢酶。此外，我们还观察到与HIV-1病毒蛋白相互作用的蛋白质丰度的变化。我们的蛋白质组学分析捕获了病毒产生时宿主蛋白环境的变化，描述了可能有助于病毒复制的细胞过程的变化。预计持续的分析将集中在通过靶向这些途径及其效应蛋白来阻断病毒复制。
Relatively little is known at the functional genomic level about the global host response to human immunodeficiency virus type 1 (HIV-1) infection. Microarray analyses by several laboratories, including our own, have revealed that HIV-1 infection causes significant changes in host mRNA abundance and regulation of several cellular biological pathways. However, it remains unclear what consequences these changes bring about at the protein level. Here we report the expression levels of similar to 3,200 proteins in the CD4+ CEMx174 cell line after infection with the LAI strain of human immunodeficiency virus type I (HIV-1); the proteins were assessed using liquid chromatography-mass spectrometry coupled with stable isotope labeling and the accurate mass and time tag approach. Furthermore, we found that 687 (21%) proteins changed in abundance at the peak of virus production at 36 h postinfection. Pathway analysis revealed that the differential expression of proteins was concentrated in select biological pathways, exemplified by ubiquitin-conjugating enzymes in ubiquitination, carrier proteins in nucleocytoplasmic transport, cyclin-dependent kinase in cell cycle progression, and pyruvate dehydrogenase of the citrate cycle pathways. Moreover, we observed changes in the abundance of proteins with known interactions with HIV-1 viral proteins. Our proteomic analysis captured changes in the host protein milieu at the time of robust virus production, depicting changes in cellular processes that may contribute to virus replication. Continuing analyses are expected to focus on blocking virus replication by targeting these pathways and their effector proteins.