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

被引:31
作者
Calvert, Julie K. [1 ]
Helbig, Karla J. [2 ]
Dimasi, David [3 ,4 ]
Cockshell, Michaelia [3 ,4 ]
Beard, Michael R. [2 ,3 ,4 ]
Pitson, Stuart M. [3 ,4 ]
Bonder, Claudine S. [3 ,4 ]
Carr, Jillian M. [1 ]
机构
[1] Flinders Univ S Australia, Sch Med, Microbiol & Infect Dis, Adelaide, SA 5042, Australia
[2] Univ Adelaide, Sch Mol & Biomed Sci, Adelaide, SA, Australia
[3] Univ S Australia, Ctr Canc Biol, Adelaide, SA 5001, Australia
[4] SA Pathol, Adelaide, SA, Australia
基金
英国医学研究理事会; 澳大利亚国家健康与医学研究理事会;
关键词
NECROSIS-FACTOR-ALPHA; HEPARAN-SULFATE; I INTERFERON; PERMEABILITY; ACTIVATION; TYPE-2; BINDING; KINASE; IDENTIFICATION; PATHOGENESIS;
D O I
10.1089/jir.2014.0195
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
070307 [化学生物学]; 071010 [生物化学与分子生物学];
摘要
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)-beta, OAS-1, IFIT-1/ISG56, and viperin mRNA. Antibody blocking of IFN-beta 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-beta 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.
引用
收藏
页码:654 / 665
页数:12
相关论文
共 68 条
[1]
Senescence Affects Endothelial Cells Susceptibility to Dengue Virus Infection [J].
AbuBakar, Sazaly ;
Shu, Meng-Hooi ;
Johari, Jefree ;
Wong, Pooi-Fong .
INTERNATIONAL JOURNAL OF MEDICAL SCIENCES, 2014, 11 (06) :538-544
[2]
Activation of endothelial cells via antibody-enhanced dengue virus infection of peripheral blood monocytes [J].
Anderson, R ;
Wang, SL ;
Osiowy, C ;
Issekutz, AC .
JOURNAL OF VIROLOGY, 1997, 71 (06) :4226-4232
[3]
REPLICATION OF DENGUE AND JUNIN VIRUSES IN CULTURED RABBIT AND HUMAN ENDOTHELIAL CELLS [J].
ANDREWS, BS ;
THEOFILOPOULOS, AN ;
PETERS, CJ ;
LOSKUTOFF, DJ ;
BRANDT, WE ;
DIXON, FJ .
INFECTION AND IMMUNITY, 1978, 20 (03) :776-781
[4]
Characterization of a Distinct Population of Circulating Human Non-Adherent Endothelial Forming Cells and Their Recruitment via Intercellular Adhesion Molecule-3 [J].
Appleby, Sarah L. ;
Cockshell, Michaelia P. ;
Pippal, Jyotsna B. ;
Thompson, Emma J. ;
Barrett, Jeffrey M. ;
Tooley, Katie ;
Sen, Shaundeep ;
Sun, Wai Yan ;
Grose, Randall ;
Nicholson, Ian ;
Levina, Vitalina ;
Cooke, Ira ;
Talbo, Gert ;
Lopez, Angel F. ;
Bonder, Claudine S. .
PLOS ONE, 2012, 7 (11)
[5]
Primary Human Endothelial Cells Support Direct But Not Antibody-Dependent Enhancement of Dengue Viral Infection [J].
Arevalo, Maria T. ;
Simpson-Haidaris, Patricia J. ;
Kou, Zhihua ;
Schlesinger, Jacob J. ;
Jin, Xia .
JOURNAL OF MEDICAL VIROLOGY, 2009, 81 (03) :519-528
[6]
Recognition of heparan sulfate by clinical strains of dengue virus serotype 1 using recombinant subviral particles [J].
Artpradit, Charlermchai ;
Robinson, Luke N. ;
Gavrilov, Boris K. ;
Rurak, Troy T. ;
Ruchirawat, Mathuros ;
Sasisekharan, Ram .
VIRUS RESEARCH, 2013, 176 (1-2) :69-77
[7]
Avirutnan P, 1998, J IMMUNOL, V161, P6338
[8]
Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E [J].
Avirutnan, Panisadee ;
Zhang, Lijuan ;
Punyadee, Nuntaya ;
Manuyakorn, Ananya ;
Puttikhunt, Chunya ;
Kasinrerk, Watchara ;
Malasit, Prida ;
Atkinson, John P. ;
Diamond, Michael S. .
PLOS PATHOGENS, 2007, 3 (11) :1798-1812
[9]
Type I interferon is a therapeutic target for virus-induced lethal vascular damage [J].
Baccala, Roberto ;
Welch, Megan J. ;
Gonzalez-Quintial, Rosana ;
Walsh, Kevin B. ;
Teijaro, John R. ;
Nguyen, Anthony ;
Ng, Cherie T. ;
Sullivan, Brian M. ;
Zarpellon, Alessandro ;
Ruggeri, Zaverio M. ;
de la Torre, Juan Carlos ;
Theofilopoulos, Argyrios N. ;
Oldstone, Michael B. A. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (24) :8925-8930
[10]
Tropism of Dengue Virus in Mice and Humans Defined by Viral Nonstructural Protein 3-Specific Immunostaining [J].
Balsitis, Scott J. ;
Coloma, Josefina ;
Castro, Glenda ;
Alava, Aracely ;
Flores, Diana ;
McKerrow, James H. ;
Beatty, P. Robert ;
Harris, Eva .
AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE, 2009, 80 (03) :416-424