GC-MS-Based Metabonomic Profiling Displayed Differing Effects of Borna Disease Virus Natural Strain Hu-H1 and Laboratory Strain V Infection in Rat Cortical Neurons.
Borna disease virus (BDV) persists in the central nervous systems of a wide variety of vertebrates and causes behavioral disorders. Previous studies have revealed that metabolic perturbations are associated with BDV infection. However, the pathophysiological effects of different viral strains remain largely unknown. Rat cortical neurons infected with human strain BDV Hu-H1, laboratory BDV Strain V, and non-infected control (CON) cells were cultured in vitro. At day 12 post-infection, a gas chromatography coupled with mass spectrometry (GC-MS) metabonomic approach was used to differentiate the metabonomic profiles of 35 independent intracellular samples from Hu-H1-infected cells (n = 12), Strain V-infected cells (n = 12), and CON cells (n = 11). Partial least squares discriminant analysis (PLS-DA) was performed to demonstrate discrimination between the three groups. Further statistical testing determined which individual metabolites displayed significant differences between groups. PLS-DA demonstrated that the whole metabolic pattern enabled statistical discrimination between groups. We identified 31 differential metabolites in the Hu-H1 and CON groups (21 decreased and 10 increased in Hu-H1 relative to CON), 35 differential metabolites in the Strain V and CON groups (30 decreased and 5 increased in Strain V relative to CON), and 21 differential metabolites in the Hu-H1 and Strain V groups (8 decreased and 13 increased in Hu-H1 relative to Strain V). Comparative metabonomic profiling revealed divergent perturbations in key energy and amino acid metabolites between natural strain Hu-H1 and laboratory Strain V of BDV. The two BDV strains differentially alter metabolic pathways of rat cortical neurons in vitro. Their systematic classification provides a valuable template for improved BDV strain definition in future studies.
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. 18983145528@163.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. 18983145528@163.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. 18983145528@163.com.
Siwen
S
Liu
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. Liv.Bode@web.de.
Liv
L
Bode
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. chongqing2012bruce@gmail.com.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. chongqing2012bruce@gmail.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. chongqing2012bruce@gmail.com.
Lujun
L
Zhang
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. hepeng000@sina.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. hepeng000@sina.com.
Peng
P
He
Department of Rehabilitation, the Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. rzhuang@live.com.
Rongzhong
R
Huang
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. tilamisu789456123@126.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. tilamisu789456123@126.com.|Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. tilamisu789456123@126.com.
Lin
L
Sun
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. iconsig@sina.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. iconsig@sina.com.
Shigang
S
Chen
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. ASDFG43215@126.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. ASDFG43215@126.com.
Hong
H
Zhang
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. g1240725344@163.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. g1240725344@163.com.|Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. g1240725344@163.com.
Yujie
Y
Guo
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. duduzjj@163.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. duduzjj@163.com.
Jingjing
J
Zhou
Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. yingyuf0311@163.com.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. yingyuf0311@163.com.
Yuying
Y
Fu
Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. zhudan25@126.com.
Dan
D
Zhu
Department of Neurology, Yongchuan Hospital, Chongqing Medical University, Chongqing 402460, China. xiepeng@cqmu.edu.cn.|Institute of Neuroscience and the Collaborative Innovation Center for Brain Science, Chongqing Medical University, Chongqing 400016, China. xiepeng@cqmu.edu.cn.|Chongqing Key Laboratory of Neurobiology, Chongqing Medical University, Chongqing 400016, China. xiepeng@cqmu.edu.cn.|Department of Neurology, the First Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China. xiepeng@cqmu.edu.cn.
Peng
P
Xie
D000818:Animals; D001890:Borna Disease / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D001891:Borna disease virus / Q000302:isolation & purification / Q000378:metabolism*; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D002478:Cells, Cultured; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D055442:Metabolome; D055432:Metabolomics; D009474:Neurons / Q000378:metabolism* / Q000473:pathology / Q000821:virology*; D051381:Rats / Q000378:metabolism / Q000821:virology*; D017207:Rats, Sprague-Dawley
GC-MS; borna disease virus; metabonomic; neuron; rat