Human but Not Laboratory Borna Disease Virus Inhibits Proliferation and Induces Apoptosis in Human Oligodendrocytes In Vitro

Abstract

Borna disease virus (BDV) is a neurotropic virus that produces neuropsychiatric dysfunction in a wide range of warm-blooded species. Several studies have associated BDV with human psychiatric illness, but the findings remain controversial. Although oligodendrocytes are a major glial component of brain white matter and play a pivotal role in neuronal cell function, BDV's effects on human oligodendrocytes have not been clarified. Here, the effects of two BDV strains, Hu-H1 (isolated from a bipolar patient) and Strain V (a laboratory strain), on the proliferation and apoptosis of human oligodendrocytes were investigated. Three experimental cell lines were constructed: Hu-H1-infected oligodendroglioma (Hu-H1) cells, Strain V-infected oligodendroglioma (Strain V) cells, and non-infected oligodendroglioma (control) cells. BDV infection was assayed by BDV nucleoprotein (p40) immunofluorescence, cell proliferation was assayed by Cell Counting Kit-8 (CCK8), and cell cycle phases and apoptosis were assayed by flow cytometry. Expressions of the apoptosis-related proteins Bax and Bcl-2 were measured by Western blotting. p40 expression was confirmed in Hu-H1 and Strain V on and after day three post-infection. Strain V cells showed significantly greater cellular proliferation than Hu-H1 cells on and after day three post-infection. In Hu-H1 cells, Bax and Bcl-2 expression were significantly increased and decreased, respectively, on and after day three post-infection. In contrast, in Strain V cells, Bax and Bcl-2 expression were significantly decreased and increased, respectively, on and after day three post-infection. In conclusion, Hu-H1 inhibits cellular proliferation and promotes apoptosis in human oligodendrocytes via Bax upregulation and Bcl-2 downregulation. In contrast, Strain V promotes cellular proliferation and inhibits apoptosis in human oligodendrocytes via Bax downregulation and Bcl-2 upregulation. The effects of the Hu-H1 strain (isolated from a bipolar patient) are opposite from those of Strain V (a laboratory strain), thereby providing a proof of authenticity for both.

Proteomics reveal energy metabolism and mitogen-activated protein kinase signal transduction perturbation in human Borna disease virus Hu-H1-infected oligodendroglial cells

“…Although neurons are the major targets of BDV, the cell spectrum in the brain includes astroglia and oligodendroglia, as well (Carbone et al, 1993). Various cell types and viral strains have been shown to differentially affect BDV's influence on the host (Williams et al, 2008;Poenisch et al, 2009;Wu et al, 2013), including our above-mentioned study (Li et al, 2013). However, a better insight into the mechanism, how BDV and the human strain in particular the human BDV strain manipulates its host cells in vitro, should support our understanding of BDV's neuropathogenesis in vivo.…”

“…Impaired translocation may at least partially explain our findings of up-regulated pERK and down-regulated proliferation in OL cells infected with a human strain of BDV. Inhibited cell proliferation was previously observed in human but not laboratory BDV (Li et al, 2013). Given the complex regulatory network between the ERK/RSK pathway, cell proliferation and programed cell death by apoptosis in multiple mammalian cell lines (for review Kurokawa and Kornbluth, 2009), the precise manner by which BDV Hu-H1's activation of the ERK-RSK complex interferes with cell proliferation and the other biological processes warrant further research.…”

“…Moreover, our previous metabonomic research has demonstrated that one of these human strains, BDV Hu-H1, which had been isolated from a severely depressed, hospitalized bipolar patient's PBMCs, perturbs energy metabolites in OL cells (Huang et al, 2012). Even more interesting, our group could have found last year that BDV Hu-H1 differed remarkably from the laboratory-adapted BDV strain V. In fact, BDV Hu-H1 inhibited proliferation and promoted apoptosis in OL cells, while strain V displayed the opposite effects (Li et al, 2013). Lab strain V was originally isolated from a diseased horse in Germany in the late 1920s, underwent numerous in vivo passages in rabbits and rats followed by multiple cell culture passaging.…”

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

“…Recently, human BDV infections have been reported in China and research into human infections BDV has been conducted (32)(33)(34)(35). BDV is known to result in behavioral disturbances in mammals, however, its effects on humans is subject to debate (5).…”

Proliferation and stemness preservation of human adipose-derived stem cells by surface-modified in situ TiO2 nanofibrous surfaces

“…As revealed from the DNA histogram in Figure 5, no evidence that aneuploidy was found on either surface since there is only a single peak in the G0/G1 phase. 33 In the cell cycle, the primary phases that are responsible for cell proliferation are the S and G2/M phases, 34 and therefore the proliferation index (sum of the percentage of cells in S and G2/M phases) was calculated to assess the cell proliferation capacity of both surfaces (Table 2). In the G0/G1 phase, TiO 2 nanofibrous surfaces showed a significantly lower percentage of cells compared to the control surfaces.…”