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

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism*
  • Borna Disease / metabolism*
  • Cells, Cultured
  • Fluorescent Antibody Technique
  • Humans
  • Oligodendroglia / metabolism*
  • Oligodendroglia / virology

Substances

  • Amino Acids

Grants and funding

This work was 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). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.