Proteomic analysis of endothelial cell autoantigens recognized by anti-dengue virus nonstructural protein 1 antibodies.
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.
Cheng
Hsien-Jen
HJ
Institute of Basic Medical Sciences, National Cheng Kung University Medical College, Tainan, Taiwan.
Lin
Chiou-Feng
CF
Lei
Huan-Yao
HY
Liu
Hsiao-Sheng
HS
Yeh
Trai-Ming
TM
Luo
Yueh-Hsia
YH
Lin
Yee-Shin
YS
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
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