Metabolic effects of influenza virus infection in cultured animal cells: Intra- and extracellular metabolite profiling.
Metabolic effects of influenza virus infection in cultured animal cells: Intra- and extracellular metabolite profiling.
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DOI：
10.1186/1752-0509-4-61
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发表时间：
2010-05-13
影响因子：
--
通讯作者：
Reichl U
中科院分区：
文献类型：
--
作者：
Ritter JB;Wahl AS;Freund S;Genzel Y;Reichl U
细胞培养衍生的流感疫苗生产的许多细节仍然知之甚少，工艺优化的方法主要仍然是经验性的。对病毒感染后哺乳动物细胞代谢的更多了解可能会提示限制和细胞特异性病毒生产能力。基于代谢物浓度的细胞外和细胞内测量，对流感感染的贴壁细胞系（MDCK）进行了详细的代谢表征。对于大多数代谢物，感染（人流感A/PR/8/34）和模拟感染细胞的比较在感染后（pi）的前10-12小时期间显示出非常相似的行为。感染后约12 h观察到显著变化：（1）与模拟感染细胞相比，感染细胞中细胞外葡萄糖的摄取和乳酸盐释放到细胞培养上清液中明显增加。同时（12 h pi）糖酵解上部的细胞内代谢物浓度显著增加。相反，感染细胞的核苷三磷酸浓度明显下降后12小时PI。两种不同的人流感A/PR/8/34毒株在略微不同的时间点观察到这种行为。将这些结果与相同流感毒株感染时程的文献值进行比较，强调了流感感染仅代表宿主细胞代谢的轻微额外负担的假设。感染后12小时观察到的代谢变化很可能是由感染细胞凋亡引起的。来自具有不同生产力和感染动力学的A/PR/8/34病毒株的两种变体（RKI与NIBSC）的实验数据的比较显示出相当的代谢模式，但具有明显不同的时间行为。因此，感染动力学明显地反映在宿主细胞代谢中。
Many details in cell culture-derived influenza vaccine production are still poorly understood and approaches for process optimization mainly remain empirical. More insights on mammalian cell metabolism after a viral infection could give hints on limitations and cell-specific virus production capacities. A detailed metabolic characterization of an influenza infected adherent cell line (MDCK) was carried out based on extracellular and intracellular measurements of metabolite concentrations. For most metabolites the comparison of infected (human influenza A/PR/8/34) and mock-infected cells showed a very similar behavior during the first 10-12 h post infection (pi). Significant changes were observed after about 12 h pi: (1) uptake of extracellular glucose and lactate release into the cell culture supernatant were clearly increased in infected cells compared to mock-infected cells. At the same time (12 h pi) intracellular metabolite concentrations of the upper part of glycolysis were significantly increased. On the contrary, nucleoside triphosphate concentrations of infected cells dropped clearly after 12 h pi. This behaviour was observed for two different human influenza A/PR/8/34 strains at slightly different time points. Comparing these results with literature values for the time course of infection with same influenza strains, underline the hypothesis that influenza infection only represents a minor additional burden for host cell metabolism. The metabolic changes observed after12 h pi are most probably caused by the onset of apoptosis in infected cells. The comparison of experimental data from two variants of the A/PR/8/34 virus strain (RKI versus NIBSC) with different productivities and infection dynamics showed comparable metabolic patterns but a clearly different timely behavior. Thus, infection dynamics are obviously reflected in host cell metabolism.
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影响因子：
3.7
作者：
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通讯作者：
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10.1016/j.bbadis.2007.08.003
发表时间：
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影响因子：
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作者：
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通讯作者：
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