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Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E
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Metadata
Document Title
Secreted NS1 of dengue virus attaches to the surface of cells via interactions with heparan sulfate and chondroitin sulfate E
Author
Avirutnan P.,Zhang L.,Punyadee N.,Manuyakorn A.,Puttikhunt C.,Kasinrerk W.,Malasit P.,Atkinson J.P.,Diamond M.S.
Name from Authors Collection
Affiliations
Department of Medicine, Washington University School of Medicine, St. Louis, MO, United States; Medical Molecular Biology Unit, Office for Research and Development, Mahidol University, Bangkok, Thailand; Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, United States; Department of Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand; Medical Biotechnology Unit, National Center for Genetic Engineering and Biotechnology BIOTEC, National Science and Technology Development Agency NSTDA, Pathumthani, Thailand; Department of Medical Technology, Faculty of Associated Medical Sciences, Chiang Mai University, Chiang Mai, Thailand; Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, MO, United States
Type
Article
Source Title
PLoS Pathogens
ISSN
15537366
Year
2007
Volume
3
Issue
11
Page
1798-1812
Open Access
All Open Access, Gold, Green
DOI
10.1371/journal.ppat.0030183
Abstract
Dengue virus (DENV) nonstructural protein-1 (NS1) is a secreted glycoprotein that is absent from viral particles but accumulates in the supernatant and on the plasma membrane of cells during infection. Immune recognition of cell surface NS1 on endothelial cells has been hypothesized as a mechanism for the vascular leakage that occurs during severe DENV infection. However, it has remained unclear how NS1 becomes associated with the plasma membrane, as it contains no membrane-spanning sequence motif. Using flow cytometric and ELISA-based binding assays and mutant cell lines lacking selective glycosaminoglycans, we show that soluble NS1 binds back to the surface of uninfected cells primarily via interactions with heparan sulfate and chondroitin sulfate E. DENV NS1 binds directly to the surface of many types of epithelial and mesenchymal cells yet attaches poorly to most peripheral blood cells. Moreover, DENV NS1 preferentially binds to cultured human microvascular compared to aortic or umbilical cord vein endothelial cells. This binding specificity was confirmed in situ as DENV NS1 bound to lung and liver but not intestine or brain endothelium of mouse tissues. Differential binding of soluble NS1 by tissue endothelium and subsequent recognition by anti-NS1 antibodies could contribute to the selective vascular leakage syndrome that occurs during severe secondary DENV infection. © 2007 Avirutnan et al.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
National Institute of General Medical Sciences
License
CC BY
Rights
Author
Publication Source
Scopus