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博尔纳病病毒感染扰乱培养的人少突胶质细胞中的能量代谢物和氨基酸。

Borna disease virus infection perturbs energy metabolites and amino acids in cultured human oligodendroglia cells.

机构信息

Department of Neurology, The First Affiliated Hospital, Chongqing Medical University, Chongqing, China.

出版信息

PLoS One. 2012;7(9):e44665. doi: 10.1371/journal.pone.0044665. Epub 2012 Sep 7.

Abstract

BACKGROUND

Borna disease virus is a neurotropic, non-cytolytic virus that has been widely employed in neuroscientific research. Previous studies have revealed that metabolic perturbations are associated with Borna disease viral infection. However, the pathophysiological mechanism underlying its mode of action remains unclear.

METHODOLOGY

Human oligodendroglia cells infected with the human strain Borna disease virus Hu-H1 and non-infected matched control cells were cultured in vitro. At day 14 post-infection, a proton nuclear magnetic resonance-based metabonomic approach was used to differentiate the metabonomic profiles of 28 independent intracellular samples from Borna disease virus-infected cells (n = 14) and matched control cells (n = 14). Partial least squares discriminant analysis was performed to demonstrate that the whole metabonomic patterns enabled discrimination between the two groups, and further statistical testing was applied to determine which individual metabolites displayed significant differences between the two groups.

FINDINGS

Metabonomic profiling revealed perturbations in 23 metabolites, 19 of which were deemed individually significant: nine energy metabolites (α-glucose, acetate, choline, creatine, formate, myo-inositol, nicotinamide adenine dinucleotide, pyruvate, succinate) and ten amino acids (aspartate, glutamate, glutamine, glycine, histidine, isoleucine, phenylalanine, threonine, tyrosine, valine). Partial least squares discriminant analysis demonstrated that the whole metabolic patterns enabled statistical discrimination between the two groups.

CONCLUSION

Borna disease viral infection perturbs the metabonomic profiles of several metabolites in human oligodendroglia cells cultured in vitro. The findings suggest that Borna disease virus manipulates the host cell's metabolic network to support viral replication and proliferation.

摘要

背景

博尔纳病病毒是一种神经嗜性、非细胞溶解病毒,已广泛应用于神经科学研究。先前的研究表明,代谢紊乱与博尔纳病病毒感染有关。然而,其作用机制的病理生理机制仍不清楚。

方法

体外培养感染人博尔纳病病毒 Hu-H1 的人少突胶质细胞和未感染的匹配对照细胞。在感染后第 14 天,采用基于质子磁共振的代谢组学方法,对 28 个独立的细胞内样本的代谢组学图谱进行区分,其中博尔纳病病毒感染细胞(n=14)和匹配对照细胞(n=14)。采用偏最小二乘判别分析(PLS-DA)证明两组之间的整体代谢模式可以区分,进一步的统计检验用于确定两组之间哪些个体代谢物存在显著差异。

结果

代谢组学分析显示,23 种代谢物发生了变化,其中 19 种被认为具有个体显著性:9 种能量代谢物(α-葡萄糖、乙酸盐、胆碱、肌酸、甲酸盐、肌醇、烟酰胺腺嘌呤二核苷酸、丙酮酸、琥珀酸盐)和 10 种氨基酸(天冬氨酸、谷氨酸、谷氨酰胺、甘氨酸、组氨酸、异亮氨酸、苯丙氨酸、苏氨酸、酪氨酸、缬氨酸)。偏最小二乘判别分析表明,两组之间的整体代谢模式可以进行统计学区分。

结论

博尔纳病病毒感染体外培养的人少突胶质细胞的代谢组学图谱发生了变化。研究结果表明,博尔纳病病毒操纵宿主细胞的代谢网络,以支持病毒的复制和增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a670/3436876/fb7e88fc9e83/pone.0044665.g001.jpg

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