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

Molecular Mimicry
Dengue Virus
Endothelial Cells
Dengue
Proteins
Antibodies
Severe Dengue
Amino Acids
Autoimmunity
Dengue Vaccines
Serum
Hemorrhage
Virus Diseases
Sequence Homology
Protein C

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases

Cite this

C-terminal region of dengue virus nonstructural protein 1 is involved in endothelial cell cross-reactivity via molecular mimicry. / Wan, Shu Wen; Lin, Chiou Feng; Chen, Mei Chun; Lei, Huan Yao; Liu, Hsiao Sheng; Yeh, Trai Ming; Liu, Ching Chuan; Lin, Yee Shin.

In: American Journal of Infectious Diseases, Vol. 4, No. 1, 2008, p. 85-91.

Research output: Contribution to journalArticle

Wan, Shu Wen ; Lin, Chiou Feng ; Chen, Mei Chun ; Lei, Huan Yao ; Liu, Hsiao Sheng ; Yeh, Trai Ming ; Liu, Ching Chuan ; Lin, Yee Shin. / C-terminal region of dengue virus nonstructural protein 1 is involved in endothelial cell cross-reactivity via molecular mimicry. In: American Journal of Infectious Diseases. 2008 ; Vol. 4, No. 1. pp. 85-91.
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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.",
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