C-terminal region of dengue virus nonstructural protein 1 is involved in endothelial cell cross-reactivity via molecular mimicry

Shu Wen Wan, Chiou Feng Lin, Mei Chun Chen, Huan Yao Lei, Hsiao Sheng Liu, Trai Ming Yeh, Ching Chuan Liu, Yee Shin Lin

研究成果: 雜誌貢獻文章

12 引文 斯高帕斯(Scopus)

摘要

Infection with dengue virus (DV) causes diseases ranging from self-limiied. dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia and bleeding are the clinical manifestations associated with dengue hemorrhage. We previously showed that anti-DV nonstructural protein 1 (NS1) antibodies (Abs) cross-reacted with endothelial cells. The potential target proteins on endothelial cell surface recognized by anti-DV NSI Abs showed sequence homology with the C-terminal amino acids (a.a.) 311-352.of DV NS1. In this study, the role of NS1 C-terminal region in dengue autoimmunity was investigated. We deleted the a.a. 277-352 of DV NS1 to prepare truncated NS1 (tNS1) and generated anti-DV tNS1 Abs in mice. The endothelial cell-binding activity of anti-DV tNS1 Abs was lower than that of anti-DV NS1 Abs. In addition, the endothelial cell-binding activity of anti-DV NS1 Abs was inhibited by preabsorption with DV NS1 but not with DV tNS1 proteins. The anti-P311 (a.a. 311-330) and anti-P331 (a.a. 331-350) titers of dengue patient sera were positively correlated with their endothelial cell-binding activity. Dengue patient sera showed lower binding activity to DV tNS1 than to DV NS1 proteins. The endothelial cell-binding activity of dengue patient sera was inhibited by preabsorption with P311 and P331. This study helps to understand the molecular mechanisms of autoimmunity mediated by anti-DV NS1 Abs and to provide the potential implications of tNS1 in dengue vaccine strategies.

原文英語
頁(從 - 到)85-91
頁數7
期刊American Journal of Infectious Diseases
4
發行號1
出版狀態已發佈 - 2008
對外發佈Yes

ASJC Scopus subject areas

  • Infectious Diseases

指紋 深入研究「C-terminal region of dengue virus nonstructural protein 1 is involved in endothelial cell cross-reactivity via molecular mimicry」主題。共同形成了獨特的指紋。

  • 引用此