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

研究成果: 雜誌貢獻文章同行評審

54 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)1797-1803
頁數7
期刊Journal of Immunology
183
發行號3
DOIs
出版狀態已發佈 - 八月 1 2009
對外發佈

ASJC Scopus subject areas

  • 免疫學
  • 醫藥 (全部)

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