Functional Proteomic Studies of Lycorine-treated MDCK Cells on Highly Pathogenic Avian Influenza H5N1 Virus Infection

Functional Proteomic Studies of Lycorine-treated MDCK Cells on Highly Pathogenic Avian Influenza H5N1 Virus Infection
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石蒜碱处理的 MDCK 细胞对高致病性禽流感 H5N1 病毒感染的功能蛋白质组学研究

DOI:
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发表时间:
2017-05
期刊:
Journal of Pharmaceutical and Biomedical Sciences
影响因子:
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通讯作者:
Yaolan Li
Yaolan Li
中科院分区:
其他
文献类型:
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作者:
Huibin Huang;Jun He;Zhaoyue Zhang;Yaolan Li

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用细胞培养中氨基酸稳定同位素标记(SILAC)蛋白质组学方法,分析了赖可林对流感病毒感染宿主细胞蛋白质水平的影响。我们总共鉴定了M/L组和H/M组的176个细胞蛋白质和188个蛋白质。M/L组和M/H组共鉴定出6 3个蛋白质呈上升或下降趋势。我们使用生物信息学方法,包括功能聚类、基因本体论和途径(KEGG)浓缩试验来发现共同调节的细胞蛋白集,将单个亚集分配给它们的生物学功能,并确定它们在病毒感染进展中的相互关系。据我们所知,这是第一次以时间依赖的方式同时描述细胞蛋白质组和病毒蛋白质组的动态变化。通过聚类分析,蛋白质丰度的时间依赖模式显示了高度动态的上调和/或下调过程。综上所述,我们的研究显示出强有力的证据表明,病毒感染在蛋白质水平上对细胞状态有重大影响。总之,我们首次提供了活性化合物石蒜碱作用的全面蛋白质谱特征,并提供了证据表明,增殖细胞核抗原代表了更有效地治疗流感感染的潜在治疗靶点。
Stable isotope labeling with amino acids in cell culture (SILAC), a proteomic method, has been used to analyze the protein level variation of influenza virus-infected host cells treated by lycocine. In total, we identified 176 cellular proteins in M/L group and 188 proteins in H/M group. Sixty-three proteins were identified with an upward or downward trend in M/L and M/H group. We employed bioinformatic approaches including functional clustering, gene ontology, and pathway (KEGG) enrichment tests to uncover co-regulated cellular protein sets, assigned the individual subsets to their biological functions, and determined their interrelation within the progression of viral infection. To our knowledge, this is the first time to describe dynamic changes of the cellular and, of note, the viral proteomes in a time dependent manner simultaneously. Through cluster analysis, time-dependent patterns of protein abundances revealed highly dynamic up- and/or down-regulation processes. Taken together, our study showed strong evidence that virus infection has a major impact on the cell status at the protein level. In conclusion, we provide the first comprehensive protein profile characterization of active compound lycorine effects, and provide evidence that PCNA represent potential therapeutic targets for more effective treatment of influenza infections.
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