Abstract
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.
Highlights
Borna disease virus (BDV) is a neurotropic, enveloped, non-segmented, negative-stranded RNA virus that causes chronic, persistent infections of neurons and glial cells
V could be considered authentic virus strains, regardless of a low genetic difference below 5%. Following these taxonomic principles of a standardized nomenclature, we for the first time introduce a systematic classification of natural BDV Hu-H1 and non-natural BDV Strain V, as proposed for Ebola virus (EBOV) natural and laboratory strains below the species level [21,22]
Through a Gas chromatography–mass spectrometry (GC–MS) metabonomic approach coupled with principal component analysis (PCA), Partial least squares discriminant analysis (PLS-DA), and orthogonal partial least-squares discriminant analysis (OPLS-DA) statistical analyses, this study revealed a set of differential metabolites that clearly distinguishes between the BDV Hu-H1, BDV Strain V, and non-infected controls
Summary
Borna disease virus (BDV) is a neurotropic, enveloped, non-segmented, negative-stranded RNA virus that causes chronic, persistent infections of neurons and glial cells. BDV infection has been reported in a range of animal species across a broad global geographic distribution [1], including. Previous studies have demonstrated that BDV can infect many mammalian species [4]. In addition to BDV, another species within the genus Bornavirus of the family. To our knowledge they have far not been subjected to metabonomic profiling Another remarkably interesting issue is that BDV is an evolutionarily very old virus with a suggested co-evolution of more than 40 million years in primate ancestor hosts up to humans [11], according to functional Endogenous Borna-like nucleoprotein (EBLNs). The impact of EBLNs in human and animal exogenous BDV infection remained as yet unclarified, and in vitro metabolomics studies are lacking as well
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