title: Proteomic analysis of endothelial cell autoantigens recognized by anti-dengue virus nonstructural protein 1 antibodies.
abstract: We previously showed the occurrence of autoimmune responses in dengue virus (DV) infection, which has potential implications for the pathogenesis of dengue hemorrhagic syndrome. In the present study, we have used a proteomic analysis to identify several candidate proteins on HMEC-1 endothelial cells recognized by anti-DV nonstructural protein 1 (NS1) antibodies. The target proteins, including ATP synthase beta chain, protein disulfide isomerase, vimentin, and heat shock protein 60, co-localize with anti-NS1 binding sites on nonfixed HMEC-1 cells using immunohistochemical double staining and confocal microscopy. The cross-reactivity of anti-target protein antibodies with HMEC-1 cells was inhibited by NS1 protein pre-absorption. Furthermore, a cross-reactive epitope on NS1 amino acid residues 311-330 (P311-330) was predicted using homologous sequence alignment. The reactivity of dengue hemorrhagic patient sera with HMEC-1 cells was blocked by synthetic peptide P311-330 pre-absorption. Taken together, our results identify putative targets on endothelial cells recognized by anti-DV NS1 antibodies, where NS1 P311-330 possesses the shared epitope.
authors.affiliation: Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
authors.forename: Hsien-Jen
authors.initials: HJ
authors.lastname: Cheng
authors.forename: Chiou-Feng
authors.initials: CF
authors.lastname: Lin
authors.forename: Huan-Yao
authors.initials: HY
authors.lastname: Lei
authors.forename: Hsiao-Sheng
authors.initials: HS
authors.lastname: Liu
authors.forename: Trai-Ming
authors.initials: TM
authors.lastname: Yeh
authors.forename: Yueh-Hsia
authors.initials: YH
authors.lastname: Luo
authors.forename: Yee-Shin
authors.initials: YS
authors.lastname: Lin
mesh_terms: D001324:Autoantigens / Q000235:genetics*; D003429:Cross Reactions; D003715:Dengue / Q000235:genetics*; D003716:Dengue Virus / Q000276:immunology*; D015180:Electrophoresis, Gel, Two-Dimensional; D000939:Epitopes / Q000032:analysis; D006801:Humans; D008565:Membrane Proteins / Q000276:immunology; D020543:Proteome; D011994:Recombinant Proteins / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000276:immunology* / Q000302:isolation & purification
chemical_list: D001324:Autoantigens; D000939:Epitopes; D008565:Membrane Proteins; C079340:NS1 protein, Dengue virus type 2; C082515:NS1 protein, dengue-1 virus; D020543:Proteome; D011994:Recombinant Proteins; D017361:Viral Nonstructural Proteins