Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/95187
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Type: Journal article
Title: Dengue virus infection of primary endothelial cells induces innate immune responses, changes in endothelial cells function and is restricted by interferon-stimulated responses
Author: Calvert, J.
Helbig, K.
Dimasi, D.
Cockshell, M.
Beard, M.
Pitson, S.
Bonder, C.
Carr, J.
Citation: Journal of Interferon and Cytokine Research, 2015; 35(8):654-665
Publisher: Mary Ann Liebert
Issue Date: 2015
ISSN: 1079-9907
1557-7465
Statement of
Responsibility: 
Julie K. Calvert, Karla J. Helbig, David Dimasi, Michaelia Cockshell, Michael R. Beard, Stuart M. Pitson, Claudine S. Bonder, and Jillian M. Carr
Abstract: Although endothelial cell (EC) infection is not widespread during dengue virus (DENV) infection in vivo, the endothelium is the site of the pathogenic effects seen in severe DENV disease. In this study, we investigated DENV infection of primary EC and defined factors that influence infection in this cell type. Consistent with in vivo findings where EC infection is infrequent, only 3%-15% of EC became productively DENV-2-infected in vitro. This low level infection could not be attributed to inhibition by heparin, EC donor variation, heterogeneity, or biological source. DENV-infection of EC was associated with induction of innate immune responses, including increased STAT1 protein, STAT1- phosphorylation, interferon (IFN)-β, OAS-1, IFIT-1/ISG56, and viperin mRNA. Antibody blocking of IFN-β inhibited the induction of OAS1, IFIT1/ISG56, and viperin while shRNA knockdown of viperin enhanced DENV-infection in EC. DENV-infection of EC resulted in increased activity of sphingosine kinase 1, a factor important in maintaining vascular integrity, and altered basal and stimulated changes in barrier integrity of DENV-infected EC monolayers. Thus, DENV productively infects only a small percentage of primary EC but this has a major influence on induction of IFN-β driven innate immune responses that can restrict infection while the EC themselves are functionally altered. These changes may have important consequences for the endothelium and are reflective of pathogenic changes associated with vascular leakage, as seen in DENV disease.
Keywords: Endothelial Cells
Humans
Dengue Virus
Proteins
Interferons
RNA, Small Interfering
Transfection
Virus Replication
Gene Expression
Phosphorylation
Time Factors
STAT1 Transcription Factor
Immunity, Innate
Human Umbilical Vein Endothelial Cells
Rights: © Mary Ann Liebert
DOI: 10.1089/jir.2014.0195
Grant ID: NHMRC
Appears in Collections:Aurora harvest 7
Molecular and Biomedical Science publications

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