Borna Disease Virus Infects Human Neural Progenitor Cells and Impairs Neurogenesis

Abstract

Understanding the complex mechanisms by which infectious agents can disrupt behavior represents a major challenge. The Borna disease virus (BDV), a potential human pathogen, provides a unique model to study such mechanisms. Because BDV induces neurodegeneration in brain areas that are still undergoing maturation at the time of infection, we tested the hypothesis that BDV interferes with neurogenesis. We showed that human neural stem/progenitor cells are highly permissive to BDV, although infection does not alter their survival or undifferentiated phenotype. In contrast, upon the induction of differentiation, BDV is capable of severely impairing neurogenesis by interfering with the survival of newly generated neurons. Such impairment was specific to neurogenesis, since astrogliogenesis was unaltered. In conclusion, we demonstrate a new mechanism by which BDV might impair neural function and brain plasticity in infected individuals. These results may contribute to a better understanding of behavioral disorders associated with BDV infection.

Nonstructural Protein NSs of Schmallenberg Virus Is Targeted to the Nucleolus and Induces Nucleolar Disorganization

“…BHK-21 cells (kindly provided by the National Reference Laboratory for Orbiviruses, Laboratory for Animal Health, ANSES, Maisons-Alfort, France) were grown in Glasgow MEM (GMEM [Sigma-Aldrich]) supplemented with tryptose phosphate broth, 10% FCS, and P-S. The ovine CPT-Tert cell line (kindly provided by David Griffiths, Moredun Research Institute, Penicuik, UK) derives from choroid plexus cells (45) and was grown in Iscove's modified Dulbecco's medium (IMDM [Sigma-Aldrich]) supplemented with 10% FCS, 1% sodium pyruvate, 1 mM nonessential amino acids, and P-S. Human neural progenitor cell cultures (hNPCs) were prepared from human fetal brains (first trimester stage [see references 46 and 47 for details]). hNPCs were maintained in advanced DMEM–F-12 (Invitrogen Life Technologies) supplemented with l -glutamine (2 mM [Gibco]), apotransferrin (0.1 mg/ml [Sigma-Aldrich]), insulin (25 μg/ml [Sigma-Aldrich]), and progesterone (6.3 ng/ml [Sigma-Aldrich]).…”

Comprehensive analysis of endogenous bornavirus-like elements in eukaryote genomes

“…BDV might act as a mutagen in infected cells. Although LINE-1 is usually silenced by a host epigenetic mechanism in somatic cells, it has been reported that LINE-1 was active in human neural progenitor cells that were permissive for BDV infection [96,97].…”

Analysis by high throughput sequencing of Specific Pathogen Free eggs

“…We also evaluated the level of detection of the transcriptome pipeline dedicated to embryos using a known virus present in databases: blinded transcriptome analysis of Vero cells infected at a very low multiplicity of infection (0.025 pfu/cell) with the Borna Disease virus, a non cytolytic enveloped RNA virus, allowed the detection of infection two days post infection. The virus was identified at the same time by immunofluorescence analysis and RT-PCR [16,17]. Our results strongly suggest that the hypothesis of productive infection of eggs with a virus even distant from known viruses is highly unlikely.…”