Evidence for Borna disease virus infection in neuropsychiatric patients in three western China provinces

Abstract

Borna disease virus (BDV) is a non-cytolytic, neurotropic RNA virus that can infect a wide variety of vertebrate species from birds and primates to humans. Several studies have been carried out to investigate whether BDV is associated with neuropsychiatric diseases. However, this association is still inconclusive. Two panels of subjects consisting of 1,679 various neuropsychiatric patients and healthy people from three western China provinces were enrolled in this study. BDV p24 or p40 RNA in peripheral blood mononuclear cells (PBMCs) were detected in the first panel of 1,481 subjects using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and cerebrospinal fluid (CSF) samples from the BDV RNA-positive individuals were subjected to BDV p24 antibodies testing by enzyme-linked immunosorbent assay (ELISA). BDV p24 or p40 RNA in PBMCs and p24 antibodies in plasma were detected in the second panel of 198 subjects by RT-qPCR and Western blot. A higher prevalence for BDV RNA was demonstrated in patients with viral encephalitis (6.70%), Guillain-Barré syndrome (6.70%), schizophrenia (9.90%) and chronic fatigue syndrome (CFS) (12.70%) compared to healthy controls in the first panel. CSF p24 antibodies were demonstrated in three viral encephalitis patients, two schizophrenia patients and two major depressive disorder (MDD) patients. The prevalences of p24 antibodies in plasma from patients with viral encephalitis (13.24%), multiple sclerosis (25.00%) and Parkinson's disease (22.73%) were significantly higher than healthy controls. This study demonstrates that BDV infection also exists in humans from three western China provinces, and suggests the involvement of the contribution of BDV in the aetiology of Chinese patients with some neuropsychiatric disorders, including viral encephalitis, schizophrenia, CFS, multiple sclerosis and Parkinson's disease.

Primary psychosis and Borna disease virus infection in Lithuania: a case control study

“…Previous studies including schizophrenic patients, either using BDV antibody or RNA detection techniques or both, had revealed highly varying prevalence rates between 2.1 % in Poland [25], 12 % in Taiwan [24], 14 % in Germany [20], up to 22 % [26] and 45 % in Japan [23]. A more recent Chinese study found 9.9 % schizophrenic patients RNA-positive by a p24 real-time RT-PCR [29]. Lack of comparability, characteristic for many interesting studies, had not allowed to evaluate correlative evidence, whatsoever, for defined psychiatric diseases and BDV infection.…”

“…Independently, the finding of endogenous Borna-like N protein elements (EBLNs) which had been integrated during million years of co-evolution into germ-lines of humans and their predecessors [15–17] promoted the “Mood virus hypothesis” linking BDV with psychiatric diseases [4, 5]. After the early finding of BDV specific antibodies (Ab) in psychiatric patients [18], further worldwide evidence could also be added by the presence of BDV-specific RNA [19–29], and importantly by isolation of infectious virus either from blood cells or brain of mentally ill patients [10, 12]. However, differing sensitivity levels of antibody and RNA techniques hampered the comparability of reported infection rates.…”

Identification of suitable reference genes for BDV-infected primary rat hippocampal neurons

“…BDV is a neurotropic that persists in the central nervous system (2), and affects infected individuals for their entire life span resulting in chronic, persistent infections of neurons and glial cells. It has been reported that BDV infects a range of animal species worldwide (3), including China (4,5). BDV infects neurons in the limbic system, and primarily in the hippocampus and the cortex, which has wide spread connections to diverse cortical areas (6).…”

Persistent human Borna disease virus infection modifies the acetylome of human oligodendroglia cells towards higher energy and transporter levels

“…BDVs-infection may induce a large spectrum of neuropsychiatric pathologies ranging from immune-mediated neurological disease to non-inflammatory behavioral alterations (Hornig et al, 2003;Ludwig and Bode, 2000;Zhang et al, 2014). According to many disease patterns notably reminiscent of symptoms observed in certain human neuropsychiatric disorders (Hornig et al, 2001), infection in human psychiatric illness has been studied since three decades, but the findings remain controversial (Bode and Ludwig, 2003;Bode et al, 1995;Hornig et al, 2012;Iwata et al, 1998;Rott et al, 1985;Zhang et al, 2013). Notwithstanding, a few human BDV strains have been isolated through co-cultivation of freshly isolated white blood cells from German psychiatric inpatients with a human fetal oligodendroglial cell line (OL cells) .…”