Molinas Andrea, Mirazimi Ali, Holm Angelika, Loitto Vesa M, Magnusson Karl-Eric, Vikström Elena
Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
Department of Laboratory Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden.
FEMS Microbiol Lett. 2016 Apr;363(8). doi: 10.1093/femsle/fnw058. Epub 2016 Mar 13.
Crimean-Congo hemorrhagic fever virus (CCHFV) is an arthropod-borne pathogen that causes infectious disease with severe hemorrhagic manifestations in vascular system in humans. The proper function of the cells in the vascular system is critically regulated by aquaporins (AQP), water channels that facilitate fluxes of water and small solutes across membranes. With Hazara virus as a model for CCHFV, we investigated the effects of viruses on AQP6 and the impact of AQP6 on virus infectivity in host cells, using transiently expressed GFP-AQP6 cells, immunofluorescent assay for virus detection, epifluorescent imaging of living cells and confocal microscopy. In GFP-AQP6 expressing cells, Hazara virus reduced both the cellular and perinuclear AQP6 distribution and changed the cell area. Infection of human cell with CCHFV strain IbAR 10200 downregulated AQP6 expression at mRNA level. Interestingly, the overexpression of AQP6 in host cells decreased the infectivity of Hazara virus, speaking for a protective role of AQP6. We suggest the possibility for AQP6 being a novel player in the virus-host interactions, which may lead to less severe outcomes of an infection.
克里米亚-刚果出血热病毒(CCHFV)是一种节肢动物传播的病原体,可导致人类血管系统出现严重出血表现的传染病。血管系统中细胞的正常功能受到水通道蛋白(AQP)的严格调控,水通道蛋白是促进水和小分子溶质跨膜流动的水通道。以哈扎拉病毒作为CCHFV的模型,我们使用瞬时表达绿色荧光蛋白(GFP)-AQP6的细胞、用于病毒检测的免疫荧光测定、活细胞落射荧光成像和共聚焦显微镜,研究了病毒对AQP6的影响以及AQP6对宿主细胞中病毒感染性的影响。在表达GFP-AQP6的细胞中,哈扎拉病毒减少了细胞内和细胞核周围的AQP6分布,并改变了细胞面积。用CCHFV毒株IbAR 10200感染人细胞会在mRNA水平下调AQP6的表达。有趣的是,在宿主细胞中过表达AQP6会降低哈扎拉病毒的感染性,这表明AQP6具有保护作用。我们认为AQP6有可能是病毒-宿主相互作用中的一个新角色,这可能导致感染的后果不那么严重。