Signal Mechanisms for Pathological Effects of Endothelial Cell Induced by Dengue NS-1 Ab and Envelop Protein Domain 3

• Main Authors: Chia-Lun Hsieh, 謝佳倫
• Other Authors: Wen-Sheng Wu
• Format: Others
• Language: zh-TW
• Published: 2014
• Online Access: http://ndltd.ncl.edu.tw/handle/80447126023051074701

碩士 === 慈濟大學 === 分子生物暨人類遺傳學系碩士班 === 102 === Dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are the most severe diseases caused by Dengue virus infection. Base on the autoAb theory, the antibodies derived from nonstructural protein-1 during secondary dengue infection may cross react with vascular endothelial cells and other target cells, exerting detrimental cellular effects that lead to DHF/DSS. This issue was further addressed by others demonstrating that NS-1 Ab could induce apoptosis of human microvascular endothelial cell line-1 (HMEC-1). However whether other dengue derived etiological agent, in accompanied with NS-1 Ab, also contribute to the development of DHF was not clear. Other investigator had proposed that DHF/DSS could be triggered by combined action of Anti-NS1 Ab and the virus itself during 2nd dengue infection (The double hit hypothesis). It had been shown that Dengue E3 (envelop protein domain 3) may also trigger apoptosis of HMEC-1. On the other hand, the researchers in our Lab found JNK activation mediated growth inhibition and apoptosis of HMEC-1 induced by the affinity purified anti-NS1 Ab. Therefore, it is tempting to speculate that E3 may enhance apoptosis of endothelial cells induced by NS-1 Abs. Recently, we used anti-NS1 Ab and recombinant soluble dengue E3 protein to treat or co-treat HMEC-1 cell. We found that either Ab or E3 protein can trigger apoptosis and growth inhibition of HMEC-1 associated with JNK activation. Interestingly, the effect of co-treatment was significant higher than that in separate treatment. We also found that treatment NS1 Ab co-treated ROS inhibitor could inhibition cell apoptosis .In the future, the signaling pathways responsible for cooperative effect of anti-NS-1 Ab and E3 protein on triggering pathological effect of HMEC-1 will be investigated in detail. Blockade of the signal pathways mediating these processes may benefit prevention of DHF/DSS.