Metabolomics Analysis Of Brain Tissue From Horses Naturally Infected With Borna Disease Virus

BackgroundBorna disease virus (BDV) is a neurotropic enveloped nonsegmented,negative-stranded RNA virus that can infect wide variety of vertebratespecies from horses, birds even to human. BDV infection has been reportedacross a broad global geographic distribution. The symptomatology inanimals ranges from asymptomatic infection, behavior abnormality, toacute meningoencephalitis. Asymptomatic infection is proven to be morefrequent than expected. A large number of epidemiological studies demonstratedthat there may be a possible association between BDV infection and certainneuropsychiatric disorders, such as schizophrenia, bipolar disorder, major depressionand viral encephalitis. However, whether BDV played an important role for etiology ofpsychiatric disorders is under debate due to the publication of contradictory results. Sofar, the molecular mechanisms of asymptomatic BDV infection remainlargely unknown.Metabolomics, the comprehensive analysis of a wide range ofnumerous low molecular weight molecules, provides a promisingperspective to generate a novel hypothesis to reveal the molecularmechanisms of pathophysiological outcomes. Metabolic profilingtechniques, such as gas/liquid chromatography/mass spectrometry(GC/MS), liquid chromatography/mass spectrometry (LC/MS) and nuclearmagnetic resonance (NMR) coupled with multivariate statistical modeling,has been increasingly used to provide valuable information on stimuli-induced biochemical perturbations including virus infection.ObjectiveTo get the broad spectrum metabolites changes of brain tissue fromhorses naturally infected with Borna disease virus, we hope to find newpossible targets to elucidate the pathogenesis of horse naturally infectedwith Borna disease virus through signifcant metabolites.Methods1.Here, a total of20horses’ brains were divided into BDV and controlgroup based on the results of RT-qPCR and Western blot.2.A gas chromatography coupled with mass spectrometry (GC/MS)metabolomic method in conjunction with multivariate statistics was used tocharacterize the metabolic changes in the horses’ brains affected byasymptomatic BDV infection.Results1.Multivariate statistical analysis showed a significant discriminationbetween BDV and control group.2.The brain of BDV group was characterized by lower levels ofD-myo-inositol-1-phosphate, glutamate, phosphoethanolamine,heptadecanoic acid, and linoleic acid in combination with higher level ofammonia.ConclusionsThese differential metabolites were mainly involved in thedisturbances of amino acid and lipids metabolism. Our findings pave theway for understanding the mechanisms of BDV natural asymptomaticinfection in hosts.