Li Dan, Lei Yang, Deng Jing, Zhou Chanjuan, Zhang Yong, Li Wenjuan, Huang Hua, Cheng Shigang, Zhang Hongzhi, Zhang Liang, Huang Rongzhong, Liu Xia, Ma Lihua, Wang Xiao, Li Juan, Xie Peng
Department of Pathology, Faculty of Basic Medicine, Chongqing Medical University, Chongqing, China ; Neuroscience Center, Key Laboratory of Neurobiology of Chongqing, Chongqing, China.
PLoS One. 2013 Jun 21;8(6):e66623. doi: 10.1371/journal.pone.0066623. Print 2013.
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.
博尔纳病病毒（BDV）是一种嗜神经病毒，可在多种温血动物中引起神经精神功能障碍。多项研究将BDV与人类精神疾病联系起来，但研究结果仍存在争议。尽管少突胶质细胞是脑白质的主要胶质成分，在神经元细胞功能中起关键作用，但BDV对人类少突胶质细胞的影响尚未阐明。在此，研究了两种BDV毒株，Hu-H1（从一名双相情感障碍患者分离）和毒株V（一种实验室毒株）对人类少突胶质细胞增殖和凋亡的影响。构建了三种实验细胞系：Hu-H1感染的少突胶质细胞瘤（Hu-H1）细胞、毒株V感染的少突胶质细胞瘤（毒株V）细胞和未感染的少突胶质细胞瘤（对照）细胞。通过BDV核蛋白（p40）免疫荧光检测BDV感染，通过细胞计数试剂盒-8（CCK8）检测细胞增殖，通过流式细胞术检测细胞周期阶段和凋亡。通过蛋白质免疫印迹法检测凋亡相关蛋白Bax和Bcl-2的表达。感染后第3天及之后，在Hu-H1和毒株V中证实了p40表达。感染后第3天及之后，毒株V细胞的细胞增殖明显高于Hu-H1细胞。在Hu-H1细胞中，感染后第3天及之后，Bax表达显著增加，Bcl-2表达显著降低。相反，在毒株V细胞中，感染后第3天及之后，Bax表达显著降低，Bcl-2表达显著增加。总之，Hu-H1通过上调Bax和下调Bcl-2抑制人类少突胶质细胞的细胞增殖并促进凋亡。相反，毒株V通过下调Bax和上调Bcl-2促进人类少突胶质细胞的细胞增殖并抑制凋亡。从双相情感障碍患者分离的Hu-H1毒株的作用与实验室毒株V的作用相反，从而为两者提供了真实性的证据。
