Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation

Hsien Jen Cheng, Huan Yao Lei, Chiou Feng Lin, Yueh Hsia Luo, Shu Wen Wan, Hsiao Sheng Liu, Trai Ming Yeh, Yee Shin Lin

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Hemorrhagic syndrome is a hallmark of severe dengue diseases. We previously suggested a mechanism of molecular mimicry in which antibodies against dengue virus (DV) nonstructural protein 1 (NS1) cross-react with platelets. In the present study, we demonstrate that protein disulfide isomerase (PDI) on the platelet surface is recognized by anti-DV NS1 antibodies. Anti-DV NS1 obtained from hyperimmunized mouse sera inhibited PDI activity and platelet aggregation, and both inhibitory effects were prevented when anti-DV NS1 antibodies were preabsorbed with PDI. Anti-PDI antibodies bound to a peptide consisting of amino acid residues 311-330 (P311-330) of NS1. This peptide was a predicted epitope analyzed by homologous sequence alignments between DV NS1 and PDI. The platelet binding activities of anti-PDI and anti-DV NS1 antibodies were both reduced by P311-330 preabsorption. Similar to the findings using anti-DV NS1, antibodies against P311-330 bound to PDI and platelets, followed by inhibition of PDI activity and platelet aggregation. Furthermore, the cross-reactivity of dengue hemorrhagic fever patient sera with platelets was reduced when patient sera were preabsorbed with PDI or P311-330. Dengue hemorrhagic fever patient sera also inhibited platelet aggregation, while PDI or P311-330 reduced this inhibitory effect. In conclusion, anti-DV NS1 antibodies cross-react with PDI on platelet surface causing inhibition of platelet aggregation, which may provide implications in dengue disease pathogenesis.

Original languageEnglish
Pages (from-to)398-406
Number of pages9
JournalMolecular Immunology
Volume47
Issue number2-3
DOIs
Publication statusPublished - Dec 2009
Externally publishedYes

Fingerprint

Protein Disulfide-Isomerases
Dengue Virus
Platelet Aggregation
Blood Platelets
Antibodies
Proteins
Severe Dengue
Peptides
Amino Acids
Serum
Molecular Mimicry
Dengue
Sequence Alignment
Sequence Homology
Blood Proteins
Epitopes

Keywords

  • Antibodies
  • Cross-reactive epitope
  • Dengue virus
  • Nonstructural protein 1
  • Platelet aggregation
  • Protein disulfide isomerase

ASJC Scopus subject areas

  • Molecular Biology
  • Immunology

Cite this

Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation. / Cheng, Hsien Jen; Lei, Huan Yao; Lin, Chiou Feng; Luo, Yueh Hsia; Wan, Shu Wen; Liu, Hsiao Sheng; Yeh, Trai Ming; Lin, Yee Shin.

In: Molecular Immunology, Vol. 47, No. 2-3, 12.2009, p. 398-406.

Research output: Contribution to journalArticle

Cheng, Hsien Jen ; Lei, Huan Yao ; Lin, Chiou Feng ; Luo, Yueh Hsia ; Wan, Shu Wen ; Liu, Hsiao Sheng ; Yeh, Trai Ming ; Lin, Yee Shin. / Anti-dengue virus nonstructural protein 1 antibodies recognize protein disulfide isomerase on platelets and inhibit platelet aggregation. In: Molecular Immunology. 2009 ; Vol. 47, No. 2-3. pp. 398-406.
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