Jennische Eva, Eriksson Charlotta E, Lange Stefan, Trybala Edward, Bergström Tomas
Department of Medical Biochemistry and Cell Biology, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
J Neurovirol. 2015 Apr;21(2):129-47. doi: 10.1007/s13365-014-0312-0. Epub 2015 Jan 21.
Herpes simplex encephalitis (HSE), targeting the limbic system, is the most common cause of viral encephalitis in the Western world. Two pathways for viral entry to the central nervous system (CNS) in HSE have been suggested: either via the trigeminal nerve or via the olfactory tract. This question remains unsettled, and studies of viral spread between the two brain hemispheres are scarce. Here, we investigated the olfactory infection as a model of infection and tropism of herpes simplex virus 1 (HSV-1), the causative agent of HSE, in the CNS of rats. Rats were instilled with HSV-1 in the right nostril and sacrificed 1-6 days post-infection, and tissues were analysed for viral spread using immunohistochemistry and quantitative PCR (qPCR). After nasal instillation, HSV-1 infected mitral cells of the olfactory bulb (OB) on the right side only, followed by limbic encephalitis. As a novel finding, the anterior commissure (AC) conveyed a rapid transmission of virus between the right and the left OB, acting as a shortcut also between the olfactory cortices. The neuronal cell population that conveyed the viral infection via the AC was positive for the water channel protein aquaporin 9 (AQP9) by immunohistochemistry. Quantification of AQP9 in cerebrospinal fluid samples of HSE patients showed increment as compared to controls. We conclude that the olfactory route and the AC are important for the spread of HSV-1 within the olfactory/limbic system of rats and furthermore, we suggest that AQP9 is involved in viral tropism and pathogenesis of HSE.
单纯疱疹病毒性脑炎（HSE）主要侵犯边缘系统，是西方世界病毒性脑炎最常见的病因。目前提出了两种单纯疱疹病毒性脑炎病毒进入中枢神经系统（CNS）的途径：要么通过三叉神经，要么通过嗅束。这个问题仍未解决，且关于病毒在两个脑半球之间传播的研究很少。在这里，我们以嗅觉感染为模型，研究单纯疱疹病毒1型（HSV-1，即HSE的病原体）在大鼠中枢神经系统中的感染和嗜性。将HSV-1滴入大鼠右鼻孔，感染后1-6天处死大鼠，使用免疫组织化学和定量PCR（qPCR）分析组织中的病毒传播情况。滴鼻后，HSV-1仅感染右侧嗅球（OB）的二尖瓣细胞，随后引发边缘性脑炎。作为一项新发现，前连合（AC）介导了病毒在右侧和左侧嗅球之间的快速传播，同时也在嗅觉皮质之间起到了捷径的作用。通过免疫组织化学发现，经前连合传播病毒感染的神经元细胞群对水通道蛋白水通道蛋白9（AQP9）呈阳性反应。对HSE患者脑脊液样本中AQP9的定量分析显示，与对照组相比有所增加。我们得出结论，嗅觉途径和前连合对于HSV-1在大鼠嗅觉/边缘系统内的传播很重要，此外，我们认为AQP9参与了HSE的病毒嗜性和发病机制。
