Dengue Virus Infection of Primary Endothelial Cells Induces Innate Immune Responses, Changes in Endothelial Cells Function and Is Restricted by Interferon-Stimulated Responses

dc.contributor.author Calvert, Julie K
dc.contributor.author Helbig, K J
dc.contributor.author Dimasi, David Paul
dc.contributor.author Cockshell, M
dc.contributor.author Beard, Michael
dc.contributor.author Pitson, S M
dc.contributor.author Bonder, Claudine
dc.contributor.author Carr, Jill
dc.date.accessioned 2015-11-03T04:02:23Z
dc.date.available 2015-11-03T04:02:23Z
dc.date.issued 2015-08-05
dc.description This is a peer reviewed post print version, the final publication is available from Mary Ann Liebert, Inc., publishers http://dx.doi.org/10.1089/jir.2014.0195. A 12 month embargo from date of publication has been placed on this article in accordance with the publishers self-archiving policy. The article will be available from 6 August 2016. en
dc.description.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. en
dc.identifier.citation Calvert JK, Helbig KJ, Dimasi D, Cockshell M, Beard MR, Pitson SM, Bonder CS, Carr JM. Dengue Virus Infection of Primary Endothelial Cells Induces InnateImmune Responses, Changes in Endothelial Cells Function and Is Restricted byInterferon-Stimulated Responses. Journal of Interferon and Cytokine Research . 2015 Aug;35(8):654-65. doi: 10.1089/jir.2014.0195. en
dc.identifier.doi https://doi.org/10.1089/jir.2014.0195 en
dc.identifier.issn 1079-9907
dc.identifier.issn 1557-7465
dc.identifier.uri http://hdl.handle.net/2328/35711
dc.language.iso en
dc.publisher Mary Ann Liebert, Inc. en
dc.relation.grantnumber AISRF06200 en
dc.rights Copyright (2015) Mary Ann Liebert, Inc. en
dc.rights.holder Mary Ann Liebert, Inc. en
dc.rights.license In Copyright
dc.title Dengue Virus Infection of Primary Endothelial Cells Induces Innate Immune Responses, Changes in Endothelial Cells Function and Is Restricted by Interferon-Stimulated Responses en
dc.type Article en
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