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.

Structure and Characterization of Crimean-Congo Hemorrhagic Fever Virus GP38

“…However, the N-linked glycosylation sites for CCHFV GP38 did not align with the putative Nlinked glycosylation sites in any of the GP38 sequences from the other viruses, suggesting they are not critical to the function of GP38. Among the viruses in the two serogroups, NSDV, Ganjam virus and Dugbe virus have been reported to cause rare incidents of human infection (18,19), whereas Hazara virus is considered non-pathogenic for humans and has been used as a model for CCHFV (20,21). We also performed ConSurf analysis based on GP38 sequences from 13 different nairovirus species in order to predict evolutionarily conserved regions on the GP38 surface ( Fig.…”

Crimean-Congo Hemorrhagic Fever: Tick-Host-Virus Interactions

“…Furthermore, it has been recently shown that the CCHFV N protein interacts with cellular chaperones of the heat shock protein 70 family (including actin), which, in association with DnaJ cofactor adapter proteins, play roles that relate to correct folding and transport of newly synthesized and misfolded proteins and to the assembly of multicomponent complexes (Surtees et al, 2016). One other protein which has been recently demonstrated to be involved in CCHFV replication is aquaporin 6, a water channel that facilitates fluxes of water and small solutes across membranes (Molinas et al, 2016). …”

Serosurvey of Crimean–Congo Hemorrhagic Fever Virus in Cattle, Mali, West Africa

“…Disease onset typically follows an incubation period of up to 7 days and is characterized by nondescript indicators including a rapid onset of high-grade fever, fatigue, cephalalgia, dizziness, photophobia, and myalgia, often with nausea, vomiting, and diarrhea. [3][4][5][6][7] Death occurs in 10-50% of cases. 8,9 This variation might be due to a certain diversity of individual and general awareness, effectiveness of the public health system, and the circulating virus strain in the different regions.…”