Basolateral Entry and Release of Crimean-Congo Hemorrhagic Fever Virus in Polarized MDCK-1 Cells

Connolly‐Andersen, Anne‐Marie; Magnusson, Karl‐Eric; Mirazimi, Alì

doi:10.1128/jvi.02070-06

Cited by 41 publications

(41 citation statements)

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“…Previously, we have shown that CCHFV does not directly target tight junctions, nor does it cause leakage in an in vitro model utilizing the Madin-Darby Canine Kidney (MDCK) epithelial cell line (12). We also found that infected moDCs activate endothelial cells, pointing to indirect targeting of the endothelium as a cause of vascular leakage (11).…”

Section: Fig 2 Activation Of Endothelial Cells Is Virus Dose Dependmentioning

confidence: 85%

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Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Connolly‐Andersen

Moll

Andersson

et al. 2011

J Virol

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Crimean-Congo hemorrhagic fever virus (CCHFV) causes viral hemorrhagic fever with high case-fatality rates and is geographically widely distributed. Due to the requirement for a biosafety level 4 (BSL-4) laboratory and the lack of an animal model, knowledge of the viral pathogenesis is limited. Crimean-Congo hemorrhagic fever (CCHF) is characterized by hemorrhage and vascular permeability, indicating the involvement of endothelial cells (ECs). The interplay between ECs and CCHFV is therefore important for understanding the pathogenesis of CCHF. In a previous study, we found that CCHFV-infected monocyte-derived dendritic cells (moDCs) activated ECs; however, the direct effect of CCHFV on ECs was not investigated. Here, we report that ECs are activated upon infection, as demonstrated by upregulation of mRNA levels for E-selectin, vascular cell adhesion molecule 1 (VCAM1), and intercellular adhesion molecule 1 (ICAM1). Protein levels and cell surface expression of ICAM1 responded in a dose-dependent manner to increasing CCHFV titers with concomitant increase in leukocyte adhesion. Furthermore, we examined vascular endothelial (VE) cadherin in CCHFVinfected ECs by different approaches. Infected ECs released higher levels of interleukin 6 (IL-6) and IL-8; however, stimulation of resting ECs with supernatants derived from infected ECs did not result in increased ICAM1 expression. Interestingly, the moDC-mediated activation of ECs was abrogated by addition of neutralizing tumor necrosis factor alpha (TNF-␣) antibody to moDC supernatants, thereby identifying this soluble mediator as the key cytokine causing EC activation. We conclude that CCHFV can exert both direct and indirect effects on ECs.

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Section: Fig 2 Activation Of Endothelial Cells Is Virus Dose Dependmentioning

confidence: 85%

“…In a previous article, we showed in an epithelial cell model of tight junctions that CCHFV does not disrupt barrier integrity, nor did infection result in internalization of critical tightjunction proteins (12). At the time, adherens junctions were not included in the study.…”

Section: Fig 2 Activation Of Endothelial Cells Is Virus Dose Dependmentioning

confidence: 99%

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Connolly‐Andersen

Moll

Andersson

et al. 2011

J Virol

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“…The virus enters and overcomes the epithelial barrier via the tick bite and enters the vascular system. The virus get inside the epithelial cells via clathrin-and cholesterol-dependent endocytosis [168], replicates in the cytoplasm and are newly formed virus are released from the cell side facing blood vessels [169]. The microtubules, a critical part of the cell cytoskeleton and migration machinery, are involved in the entering, replication and assembly of the virus in the cytoplasm, as well as in the viral exit of the host cell [170].…”

Section: Virusmentioning

confidence: 99%

Aquaporins in Infection and Inflammation

Holm¹

2016

Linköping University Medical Dissertations

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About the cover:The front cover displays a human, blood-derived macrophage stained for aquaporin 9.During the course of the research underlying this thesis, Angelika Holm was enrolled in Forum Scientium, a multidisciplinary doctoral programme at Linköping University Printed by LiU-Tryck, Linköping, Sweden, 2016 "Be brave, even if you're not, pretend to be. No one can tell the difference."To that young, awkward, tall girl who dared to dream of something else, something more:You did it. SUPERVISOR Elena VikströmDepartment of Clinical and Experimental Medicine Linköping University Linköping Sweden When cells of the innate immune system encounter pathogens they need to respond and prepare for migration and phagocytosis and do so through volume regulatory processes. The Gramnegative bacterium Pseudomonas aeruginosa utilizes a small molecule-based communication system, called quorum sensing (QS) to control the production of its virulence factors and biofilms. We found that P. aeruginosa with a complete QS system elicits a stronger phagocytic response in human blood-derived macrophages compared to its lasI-/rhlI-mutant lacking the production of the QS molecules N-butyryl-L-homoserine lactone (C4-HSL) and N-3-oxododecanoyl-L-homoserine lactone (3O-C12-HSL). Infection with P. aeruginosa further increases the expression of AQP9 and induces re-localisation of AQP9 to the front and trailing ends of macrophages. Moreover, the 3O-C12-HSL alone elevates the expression of AQP9, redistribute the water channel to the front and rear ends and increases the cell area and volume of macrophages. Both infection with the wild type P. aeruginosa and the treatment with 3O-C12-HSL change the nano-structural architecture of the AQP9 distribution in macrophages. ASSISTANT SUPERVISORS Karl-Eric MagnussonViruses use the intracellular machinery of the invaded cells to produce and assemble new viral bodies. Intracellular AQPs are localised in a membranes of cellular organelles to regulate their function and morphology. C3H10T1/2 fibroblasts transiently expressing green fluorescent protein (GFP)-AQP6 show a reduced expression of AQP6 after Hazara virus infection and an increased cell area. Overexpressing AQP6 in C3H10T1/2 cells reduces the infectivity of Hazara virus indicating that AQP6 expression has a protective role in virus infections.Ion and water channels in the epithelial cell lining tightly regulate the water homeostasis. In microscopic colitis (MC), patients suffer from severe watery diarrhoeas. For the first time, we have shown that the expression of AQP1, 8 and 11 and the sodium/hydrogen exchanger NHE1 are reduced in colonic biopsies from MC patients compared to healthy control individuals. Following treatment with the glucocorticoid budesonide the patients experienced a rapid recovery and we observed a restored or increased expression of the AQPs and NHE1 during treatment, suggesting a role for AQPs in the diarrhoeal mechanisms in MC.Taken together, this thesis provides new evidence on the importance of water homeostasis regulatio...

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“…In contrast, depleting Huh-7.5 cells of calcium had no effect on HCVpp or HCVcc infectivity, consistent with our observation that these cells do not form TJ-dependent paracellular barriers. Many viruses exhibit polarized routes of entry into primary and transformed epithelial cells, including vaccinia virus (37), VSV (8,20,40), human cytomegalovirus (18), Crimean-Congo hemorrhagic fever virus (12), coxsackievirus B, and adenovirus (14,15). Polarized entry can be mediated by several mechanisms, such as differential distribution of viral receptors on apical and basolateral surfaces, inaccessibility or inactivation of viral receptors, and postentry factors inhibiting viral replication.…”

Section: Vol 82 2008 Role Of Polarization In Hcv Entry 467mentioning

confidence: 99%

Effect of Cell Polarization on Hepatitis C Virus Entry

Mee

Grove

Harris

et al. 2008

J Virol

104

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The primary reservoir for hepatitis C virus (HCV) replication in vivo is believed to be hepatocytes within the liver. Three host cell molecules have been reported to be important entry factors for receptors for HCV: the tetraspanin CD81, scavenger receptor BI (SR-BI), and the tight-junction (TJ) protein claudin 1 (CLDN1). The recent discovery of a TJ protein as a critical coreceptor highlighted the importance of studying the effect(s) of TJ formation and cell polarization on HCV entry. The colorectal adenocarcinoma Caco-2 cell line forms polarized monolayers containing functional TJs and was found to express the CD81, SR-BI, and CLDN1 proteins. Viral receptor expression levels increased upon polarization, and CLDN1 relocalized from the apical pole of the lateral cell membrane to the lateral cell-cell junction and basolateral domains. In contrast, expression and localization of the TJ proteins ZO-1 and occludin 1 were unchanged upon polarization. HCV infected polarized and nonpolarized Caco-2 cells to comparable levels, and entry was neutralized by anti-E2 monoclonal antibodies, demonstrating glycoprotein-dependent entry. HCV pseudoparticle infection and recombinant HCV E1E2 glycoprotein interaction with polarized Caco-2 cells occurred predominantly at the apical surface. Disruption of TJs significantly increased HCV entry. These data support a model where TJs provide a physical barrier for viral access to receptors expressed on lateral and basolateral cellular domains.Hepatitis C virus (HCV) is an enveloped positive-stranded RNA virus and the sole member of the Hepacivirus genus, within the family Flaviviridae. Worldwide, approximately 170 million individuals are infected with HCV and a significant fraction of these people are at risk of developing serious progressive liver disease. The principal reservoir for viral replication is believed to be hepatocytes within the liver. The recent development of the retrovirus pseudoparticle system (HCVpp) (5, 25) and the ability of the JFH-1 strain of HCV to release infectious particles in cell culture (HCVcc) (30,45,51) have allowed studies on the mechanism of HCV entry and replication.Viruses initiate infection by attaching to molecules or receptors on the cell surface. Expression and localization of these receptors are often important determinants of a cell's susceptibility to infection and of virus tropism for particular tissues. The observation that HCVpp only infect human liver-derived cell lines in vitro suggests that liver-specific receptors contribute to defining the hepatotropism of HCV. Current evidence suggests that at least three host cell molecules are important for HCV entry in vitro, i.e., the tetraspanin CD81 (5, 25, 35), scavenger receptor class B member I (SR-BI) (5,23,26,39), and tight-junction (TJ) protein claudin 1 (CLDN1) (19). Recent data suggest that CLDN6 and CLDN9 can also function as coreceptors allowing HCV entry (33, 50). HCV glycoproteins (gps) have been reported to interact directly with CD81 and SR-BI (reviewed in reference 11). Mutagenesis...

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Basolateral Entry and Release of Crimean-Congo Hemorrhagic Fever Virus in Polarized MDCK-1 Cells

Abstract: Crimean-Congo hemorrhagic fever virus (CCHFV) is

Cited by 41 publications

References 40 publications

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Crimean-Congo Hemorrhagic Fever Virus Activates Endothelial Cells

Aquaporins in Infection and Inflammation

Effect of Cell Polarization on Hepatitis C Virus Entry

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