Role of dengue viral envelope protein domain III in dengue induced coagulopathy and vasculopathy

• Main Authors: Jhen-cheng Wu, 吳振誠
• Other Authors: Hsin-hou Chang
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/17811446566053071078

碩士 === 慈濟大學 === 分子生物及細胞生物研究所 === 96 === Dengue virus , a member of the flavivirus family , causes an emerging global health threat. Infection of dengue virus can result a range of clinical symptoms, the more severe forms are DHF/DSS, which are characterized by thrombocytopenia, hemorrhagic manifestations and evidence of increased vascular permeability；however, the mechanisms of DHF or DSS development are not completely understood. In this study, we found that purified recombinant soluble dengue envelope protein domain III (rsEIII) bound to human platelet directly, and sequently induced platelet activation as measured by P-selectin expression on flow cytometry. Treatment of rsEIII can induce thrombocytopenia and leukopenia in B6 mice, wich were similar to clinical sign observed at early stage of dengue virus infection patients. Data from activated partial thrombin time ( aPPT ) assay showed that rsEIII could also neutralize heparin function and prolong plasma clotting time similar to the usage of protamine, a heparin antidote for clinical use. At the same time, we also found rsEIII has antiangiogenic effect as observed it’s can inhibit endothelial survival and impaired VEGF165 mediate endothelial cell proliferation in vitro and chorioallantoic membrane assay in vivo. These data suggest that dengue EIII protein region might be an important role in dengue-induced coagulopathy and vasculopathy.