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Molecular mimicry of human endothelial cell antigen by autoantibodies to nonstructural protein 1 of dengue virus.
J Biol Chem. 2011 Mar 18; 286(11):9726-36.JB

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+Show Affiliations

Graduate Institute of Life Sciences, National Defense Medical Center, Taipei 114, Taiwan.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21233208

Citation

Liu, I-Ju, et al. "Molecular Mimicry of Human Endothelial Cell Antigen By Autoantibodies to Nonstructural Protein 1 of Dengue Virus." The Journal of Biological Chemistry, vol. 286, no. 11, 2011, pp. 9726-36.
Liu IJ, Chiu CY, Chen YC, et al. Molecular mimicry of human endothelial cell antigen by autoantibodies to nonstructural protein 1 of dengue virus. J Biol Chem. 2011;286(11):9726-36.
Liu, I. J., Chiu, C. Y., Chen, Y. C., & Wu, H. C. (2011). Molecular mimicry of human endothelial cell antigen by autoantibodies to nonstructural protein 1 of dengue virus. The Journal of Biological Chemistry, 286(11), 9726-36. https://doi.org/10.1074/jbc.M110.170993
Liu IJ, et al. Molecular Mimicry of Human Endothelial Cell Antigen By Autoantibodies to Nonstructural Protein 1 of Dengue Virus. J Biol Chem. 2011 Mar 18;286(11):9726-36. PubMed PMID: 21233208.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Molecular mimicry of human endothelial cell antigen by autoantibodies to nonstructural protein 1 of dengue virus. AU - Liu,I-Ju, AU - Chiu,Chien-Yu, AU - Chen,Yun-Ching, AU - Wu,Han-Chung, Y1 - 2011/01/13/ PY - 2011/1/15/entrez PY - 2011/1/15/pubmed PY - 2011/5/17/medline SP - 9726 EP - 36 JF - The Journal of biological chemistry JO - J Biol Chem VL - 286 IS - 11 N2 - 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. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/21233208/Molecular_mimicry_of_human_endothelial_cell_antigen_by_autoantibodies_to_nonstructural_protein_1_of_dengue_virus_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0021-9258(20)51856-5 DB - PRIME DP - Unbound Medicine ER -