title: Protective role of host aquaporin 6 against Hazara virus, a model for Crimean-Congo hemorrhagic fever virus infection.
abstract: 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.
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Andrea
authors.initials: A
authors.lastname: Molinas
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, SE-171 77 Stockholm, Sweden.
authors.forename: Ali
authors.initials: A
authors.lastname: Mirazimi
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Angelika
authors.initials: A
authors.lastname: Holm
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Vesa M
authors.initials: VM
authors.lastname: Loitto
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden.
authors.forename: Karl-Eric
authors.initials: KE
authors.lastname: Magnusson
authors.affiliation: Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, SE-581 85 Linköping, Sweden elena.vikstrom@liu.se.
authors.forename: Elena
authors.initials: E
authors.lastname: Vikström
mesh_terms: D000818:Animals; D051403:Aquaporin 6 / Q000096:biosynthesis* / Q000235:genetics; D002460:Cell Line; D049452:Green Fluorescent Proteins; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000235:genetics / Q000472:pathogenicity*; D006479:Hemorrhagic Fever, Crimean / Q000473:pathology* / Q000821:virology; D054884:Host-Pathogen Interactions / Q000502:physiology*; D006801:Humans; D051379:Mice; D008809:Mice, Inbred C3H; D012333:RNA, Messenger / Q000096:biosynthesis; D014779:Virus Replication / Q000502:physiology*
chemical_list: D051403:Aquaporin 6; D012333:RNA, Messenger; D049452:Green Fluorescent Proteins
keywords: Crimean–Congo hemorrhagic fever virus; Nairovirus; aquaporin; host–virus interactions; virus infectivity; water homeostasis