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Secreted NS1 Protects Dengue Virus from Mannose-Binding Lectin-Mediated Neutralization
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Document Title
Secreted NS1 Protects Dengue Virus from Mannose-Binding Lectin-Mediated Neutralization
Author
Thiemmeca S, Tamdet C, Punyadee N, Prommool T, Songjaeng A, Noisakran S, Puttikhunt C, Atkinson JP, Diamond MS, Ponlawat A, Avirutnan P
Name from Authors Collection
Affiliations
Mahidol University; Mahidol University; National Science & Technology Development Agency - Thailand; National Center Genetic Engineering & Biotechnology (BIOTEC); Washington University (WUSTL); Washington University (WUSTL); Washington University (WUSTL); United States Department of Defense; United States Army; Walter Reed Army Institute of Research (WRAIR); Armed Forces Research Institute of Medical Science (AFRIMS)
Type
Article
Source Title
JOURNAL OF IMMUNOLOGY
Year
2016
Volume
197
Issue
10
Page
4053-4065
Open Access
Green Accepted, Bronze
Publisher
AMER ASSOC IMMUNOLOGISTS
DOI
10.4049/jimmunol.1600323
Format
Abstract
Flavivirus nonstructural protein 1 (NS1) is a unique secreted nonstructural glycoprotein. Although it is absent from the flavivirus virion, intracellular and extracellular forms of NS1 have essential roles in viral replication and the pathogenesis of infection. The fate of NS1 in insect cells has been more controversial, with some reports suggesting it is exclusively cell associated. In this study, we confirm NS1 secretion from cells of insect origin and characterize its physical, biochemical, and functional properties in the context of dengue virus (DENV) infection. Unlike mammalian cell-derived NS1, which displays both high mannose and complex type N-linked glycans, soluble NS1 secreted from DENV-infected insect cells contains only high mannose glycans. Insect cell-derived secreted NS1 also has different physical properties, including smaller and more heterogeneous sizes and the formation of less stable NS1 hexamers. Both mammalian and insect cell-derived NS1 bind to complement proteins C1s, C4, and C4-binding protein, as well as to a novel partner, mannose-binding lectin. Binding of NS1 to MBL protects DENV against mannose-binding lectin-mediated neutralization by the lectin pathway of complement activation. As we detected secreted NS1 and DENV together in the saliva of infected Aedes aegypti mosquitoes, these findings suggest a mechanism of viral immune evasion at the very earliest phase of infection.
Industrial Classification
Knowledge Taxonomy Level 1
Knowledge Taxonomy Level 2
Knowledge Taxonomy Level 3
Funding Sponsor
Faculty of Medicine Siriraj Hospital, Mahidol University [R015633003]; Thailand Research Fund [RSA 5680049]; National Institutes of Health [R01 AI077955]; Siriraj Chalermprakiat Grant from the Faculty of Medicine, Siriraj Hospital, Mahidol University; Research Lecturer Grant from the Faculty of Medicine, Siriraj Hospital, Mahidol University; Royal Golden Jubilee Ph.D. Program [PHD/0101/2554]; NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U01AI077955] Funding Source: NIH RePORTER
License
Copyright
Rights
The American Association of Immunologists, Inc.
Publication Source
WOS