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

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)85-91
Number of pages7
JournalAmerican Journal of Infectious Diseases
Volume4
Issue number1
Publication statusPublished - 2008
Externally publishedYes

    Fingerprint

Keywords

  • Autoantibody
  • Dengue virus
  • Endothelial cells
  • Molecular mimicry
  • NS1

ASJC Scopus subject areas

  • Infectious Diseases

Cite this