Molecular mimicry of human endothelial cell antigen by autoantibodies to nonstructural protein 1 of dengue virus.

  • Liu I
  • Chiu C
  • Chen Y
 et al. 
  • 27

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Abstract

The pathogenesis of dengue hemorrhagic fever and dengue shock syndrome (DHF/DSS), both serious complications of dengue virus (DV) infection, remains unclear. In this study, we found that anti-DV NS1 (nonstructural protein 1) polyclonal antibodies cross-reacted with human umbilical vein endothelial cells (HUVECs). We further identified a complex-specific mAb, DB16-1, which could recognize DV NS1 and cross-react with HUVECs and human blood vessels. The target protein of DB16-1 was further purified by immunoaffinity chromatography. LC-MS/MS analysis and co-immunoprecipitation revealed that the target protein of DB16-1 was human LYRIC (lysine-rich CEACAM1 co-isolated). Our newly generated anti-LYRIC mAbs bound to HUVECs in a pattern similar to that of DB16-1. The B-cell epitope of DB16-1 displayed a consensus motif, Lys-X-Trp-Gly (KXWG), which corresponded to amino acid residues 116-119 of DV NS1 and mimicked amino acid residues 334-337 in LYRIC. Moreover, the binding activity of DB16-1 in NS1 of DV-2 and in LYRIC disappeared after the KXWG epitope was deleted in each. In conclusion, DB16-1 targeted the same epitope in DV NS1 and LYRIC protein on human endothelial cells, suggesting that it might play a role in the pathogenesis of DHF/DSS. Future studies on the role of the anti-NS1 antibody in causing vascular permeability will undoubtedly be performed on sera collected from individuals before, during, and after the endothelial cell malfunction phase of a dengue illness.

Author-supplied keywords

  • antibodies
  • dengue
  • dengue fever
  • dengue hemorrhagic fever and
  • df
  • dhf
  • dss
  • endothelium
  • flavi viruses
  • immunology
  • lyric
  • lysine-rich ceacam1 co-isolated
  • molecular mimicry
  • nonstructural protein 1
  • ns1
  • rna viruses
  • shock syndrome

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Authors

  • I-Ju Liu

  • Chien-Yu Chiu

  • Yun-Ching Chen

  • Han-Chung Wu

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