C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry
- 1 Institute of Basic Medical Sciences, Taiwan
- 2 Institute of Clinical Medicine, Taiwan
- 3 National Cheng Kung University Medical College, Taiwan
Abstract
Infection with dengue virus (DV) causes diseases ranging from self-limited dengue fever to life-threatening dengue hemorrhagic fever and dengue shock syndrome. Vascular leakage, thrombocytopenia and bleeding are the clinical manifestations associated with dengue hemorrhage. We previously showed that anti-DV nonstructural protein 1 (NS1) antibodies (Abs) cross-reacted with endothelial cells. The potential target proteins on endothelial cell surface recognized by anti-DV NS1 Abs showed sequence homology with the C-terminal amino acids (a.a.) 311-352 of DV NS1. In this study, the role of NS1 C-terminal region in dengue autoimmunity was investigated. We deleted the a.a. 277-352 of DV NS1 to prepare truncated NS1 (tNS1) and generated anti-DV tNS1 Abs in mice. The endothelial cell-binding activity of anti-DV tNS1 Abs was lower than that of anti-DV NS1 Abs. In addition, the endothelial cell-binding activity of anti-DV NS1 Abs was inhibited by preabsorption with DV NS1 but not with DV tNS1 proteins. The anti-P311 (a.a. 311-330) and anti-P331 (a.a. 331-350) titers of dengue patient sera were positively correlated with their endothelial cell-binding activity. Dengue patient sera showed lower binding activity to DV tNS1 than to DV NS1 proteins. The endothelial cell-binding activity of dengue patient sera was inhibited by preabsorption with P311 and P331. This study helps to understand the molecular mechanisms of autoimmunity mediated by anti-DV NS1 Abs and to provide the potential implications of tNS1 in dengue vaccine strategies.
DOI: https://doi.org/10.3844/ajidsp.2008.85.91
Copyright: © 2008 Shu-Wen Wan, Chiou-Feng Lin, Mei-Chun Chen, Huan-Yao Lei, Hsiao-Sheng Liu, Trai-Ming Yeh, Ching-Chuan Liu and Yee-Shin Lin. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Keywords
- Autoantibody
- dengue virus
- endothelial cells
- molecular mimicry
- NS1