title: Molecular mimicry of human endothelial cell antigen by autoantibodies to nonstructural protein 1 of dengue virus.
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.
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.
authors.forename: I-Ju
authors.initials: IJ
authors.lastname: Liu
authors.forename: Chien-Yu
authors.initials: CY
authors.lastname: Chiu
authors.forename: Yun-Ching
authors.initials: YC
authors.lastname: Chen
authors.forename: Han-Chung
authors.initials: HC
authors.lastname: Wu
mesh_terms: D000818:Animals; D058846:Antibodies, Monoclonal, Murine-Derived / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D000956:Antigens, Viral / Q000276:immunology*; D001323:Autoantibodies / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology; D002199:Capillary Permeability / Q000276:immunology; D015815:Cell Adhesion Molecules / Q000276:immunology*; D002478:Cells, Cultured; D003715:Dengue / Q000150:complications / Q000276:immunology*; D003716:Dengue Virus / Q000276:immunology*; D042783:Endothelial Cells / Q000276:immunology*; D018604:Epitope Mapping; D000939:Epitopes / Q000276:immunology; D006801:Humans; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D018716:Molecular Mimicry / Q000276:immunology*; D016601:RNA-Binding Proteins; D014471:Umbilical Veins / Q000276:immunology*; D017361:Viral Nonstructural Proteins / Q000276:immunology*
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D000914:Antibodies, Viral; D000956:Antigens, Viral; D001323:Autoantibodies; D001324:Autoantigens; D015815:Cell Adhesion Molecules; D000939:Epitopes; C483039:MTDH protein, human; D008565:Membrane Proteins; D016601:RNA-Binding Proteins; D017361:Viral Nonstructural Proteins