Non-Cytopathic Bovine Viral Diarrhea Virus Infection Inhibits Differentiation of Bovine Neural Stem/progenitor Cells into Astrocytes in Vitro

Abstract

ABSTRACT. Bovine viral diarrhea virus (BVDV) causes fetal brain malformations in ruminants when the fetuses are infected transplacentally in mid-pregnancy. In both cytopathic and non-cytopatic virus infections, viral lytic infection in actively replicating cells and interruption of vascular integrity have been suggested as the pathogenesis, but functional disturbance of infected neural developing cells has been unclear. In this study, we examined the effect of infection with non-cytopathic BVDV2 on the differentiation of neural stem/precursor cells isolated from the bovine fetus. In the process of differentiation to three types of neural cells, neurons, astrocytes and oligodendrocytes, virus infection significantly and selectively inhibited the differentiation of neural stem/precursor cells into the astrocytic lineage. This inhibition is possibly important for the pathogenesis of congenital brain malformations associated with non-cytopathic BVDV infection.KEY WORDS: astrocyte, bovine viral diarrhea virus, central nervous system, differentiation, neural stem cell.

Neural Stem Cells: What Happens When They Go Viral?

“…For example, HSV infection of NSCs decreases neuronal differentiation and shifts fate to the glial lineage [ 46 , 60 ], while BDV infection decreases neuronal differentiation with no impact on the glial lineage [ 2 , 83 ]. Commitment to the astroglial lineage is blocked by bovine viral diarrhea virus (BVDV) infection, whereas no changes were seen in the neuronal or oligodendroglial lineages [ 84 ]. JEV and CMV can inhibit both neuronal and glial differentiation, although Kosugi et al showed that CMV inhibits neuronal lineage more profoundly [ 1 , 5 , 30 , 31 , 85 ].…”