TY  - JOUR
AU  - Wan, Shu-Wen 
AU  - Lin, Chiou-Feng 
AU  - Chen, Mei-Chun 
AU  - Lei, Huan-Yao 
AU  - Liu, Hsiao-Sheng 
AU  - Yeh, Trai-Ming 
AU  - Liu, Ching-Chuan 
AU  - Lin, Yee-Shin 
PY  - 2008
TI  - C-Terminal Region of Dengue Virus Nonstructural Protein 1 Is Involved in Endothelial Cell Cross-Reactivity via Molecular Mimicry
JF  - American Journal of Infectious Diseases
VL  - 4
IS  - 1
DO  - 10.3844/ajidsp.2008.85.91
UR  - https://thescipub.com/abstract/ajidsp.2008.85.91
AB  - 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.