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Dynamic 1H NMR-based extracellular metabonomic analysis of oligodendroglia cells infected with herpes simplex virus type 1

Abstract

Herpes simplex virus type 1 (HSV-1) is a large, neurotropic, double-stranded DNA virus that establishes a lifelong latent infection in neurons and glial cells. Previous studies reveal that several metabolic perturbations are associated with HSV-1 infection. However, the extracellular metabolic alterations associated with HSV-1 infection have not been systematically profiled in human cells. Here, a proton nuclear magnetic resonance-based metabonomic approach was applied to differentiate the extracellular metabonomic profiles of HSV-1 infected human oligodendroglia cells (n = 18) and matched control cells (n = 18) at three time points (12, 24, and 36 h post-infection). Resulting spectra were analyzed by chemometric and statistical methods. Metabonomic profiling revealed perturbations in 21 extracellular metabolites. Partial least squares discriminant analysis demonstrated that the whole metabolic patterns enabled statistical discrimination between HSV-1 infected human oligodendroglia cells and control cells. Eight extracellular metabolites, seven of which were amino acids, were primarily responsible for score plot discrimination between HSV-1 infected human oligodendroglia cells and control cells at 36 h post-infection: alanine, glycine, isoleucine, leucine, glutamate, glutamine, histidine, and lactate. HSV-1 infection alters amino acid metabolism in human oligodendroglia cells cultured in vitro. HSV-1 infection may disturb these host cellular pathways to support viral replication. Through elucidating the extracellular metabolic changes incident to HSV-1 infection, this study also provides future directions for investigation into the pathogenic mechanism of HSV-1.

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Acknowledgments

We sincerely thank Dr. N.D. Melgiri for his assistance in editing and proofreading the manuscript. This work was financially supported by the National Basic Research Program of China (973 Program) (Grant No. 2009CB918300), the National Natural Science Foundation of China (Grant No. 30900456 and 21175099), and the Natural Science Foundation Project of Chongqing (CSTC, 2008BB5238 and 2010BB5393).

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Correspondence to Xie Peng.

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Rongzhong Huang, Hongchang Gao and Lihua Ma contributed equally to this study.

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Huang, R., Gao, H., Ma, L. et al. Dynamic 1H NMR-based extracellular metabonomic analysis of oligodendroglia cells infected with herpes simplex virus type 1. Metabolomics 10, 33–41 (2014). https://doi.org/10.1007/s11306-013-0548-3

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  • DOI: https://doi.org/10.1007/s11306-013-0548-3

Keywords

  • Herpes simplex virus type 1
  • HSV-1
  • Metabonomic
  • Metabolomic
  • Metabolic
  • Oligodendroglia