Deletion of the C-terminal region of dengue virus nonstructural protein 1 (NS1) abolishes anti-NS1-mediated platelet dysfunction and bleeding tendency

Mei Chun Chen, Chiou Feng Lin, Huan Yao Lei, Shih Chao Lin, Hsiao Sheng Liu, Trai Ming Yeh, Robert Anderson, Yee Shin Lin

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

The mechanisms underlying dengue hemorrhagic disease are incompletely understood. We previously showed that antidengue virus (DV) nonstructural protein 1 (NS1) Abs cross-react with human platelets and inhibit platelet aggregation. Based on sequence homology alignment, the cross-reactive epitopes reside in the C-terminal region of DV NS1. In this study, we compared the effects of Abs against full-length DV NS1 and NS1 lacking the C-terminal aa 271 to 352 (designated ΔC NS1). Anti-ΔC NS1 Abs exhibited lower platelet binding activity than that of anti-full-length NS1. Anti-full-length NS1 but not anti-ΔC NS1 Abs inhibited platelet aggregation, which was shown to involve integrin αIIbβ3 inactivation. We found that the bleeding time in full-length NS1-hyperimmunized mice was longer than that in the normal control mice. By contrast, ΔC NS1-hyperimmunized mice showed a bleeding time similar to that of normal control mice. Passively administered anti-DV NS1, but not anti-ΔC NS1, Ab level decreased markedly in serum and this decrease was correlated with Ab binding to platelets. A transient platelet loss in the circulation was observed after anti-DV NS1, but not anti-ΔC NS1, Ab administration. In summary, platelet dysfunction and bleeding tendency are induced by anti-full-length DV NS1 but not by anti-ΔC NS1 Abs. These findings may be important not only for understanding dengue hemorrhagic disease pathogenesis but also for dengue vaccine development.

Original languageEnglish
Pages (from-to)1797-1803
Number of pages7
JournalJournal of Immunology
Volume183
Issue number3
DOIs
Publication statusPublished - Aug 1 2009
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

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