Secreted NS1 protects dengue virus from mannose-binding lectin-mediated neutralization

Somchai Thiemmeca, Chamaiporn Tamdet, Nuntaya Punyadee, Tanapan Prommool, Adisak Songjaeng, Sansanee Noisakran, Chunya Puttikhunt, John P. Atkinson, Michael S. Diamond, Alongkot Ponlawat, Panisadee Avirutnan

Research output: Contribution to journalArticle

21 Scopus citations

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 mannosebinding 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.

Original languageEnglish
Pages (from-to)4053-4065
Number of pages13
JournalJournal of Immunology
Volume197
Issue number10
DOIs
StatePublished - Nov 15 2016

Fingerprint Dive into the research topics of 'Secreted NS1 protects dengue virus from mannose-binding lectin-mediated neutralization'. Together they form a unique fingerprint.

  • Cite this

    Thiemmeca, S., Tamdet, C., Punyadee, N., Prommool, T., Songjaeng, A., Noisakran, S., Puttikhunt, C., Atkinson, J. P., Diamond, M. S., Ponlawat, A., & Avirutnan, P. (2016). Secreted NS1 protects dengue virus from mannose-binding lectin-mediated neutralization. Journal of Immunology, 197(10), 4053-4065. https://doi.org/10.4049/jimmunol.1600323