Avirutnan Panisadee, Punyadee Nuntaya, Noisakran Sansanee, Komoltri Chulaluk, Thiemmeca Somchai, Auethavornanan Kusuma, Jairungsri Aroonroong, Kanlaya Rattiyaporn, Tangthawornchaikul Nattaya, Puttikhunt Chunya, Pattanakitsakul Sa-Nga, Yenchitsomanus Pa-Thai, Mongkolsapaya Juthathip, Kasinrerk Watchara, Sittisombut Nopporn, Husmann Matthias, Blettner Maria, Vasanawathana Sirijitt, Bhakdi Sucharit, Malasit Prida
Medical Molecular Biology Unit, Siriraj Hospital, Mahidol University, Bangkok, Thailand.
J Infect Dis. 2006 Apr 15;193(8):1078-88. doi: 10.1086/500949. Epub 2006 Mar 9.
Vascular leakage and shock are the major causes of death in patients with dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Thirty years ago, complement activation was proposed to be a key underlying event, but the cause of complement activation has remained unknown.
The major nonstructural dengue virus (DV) protein NS1 was tested for its capacity to activate human complement in its membrane-associated and soluble forms. Plasma samples from 163 patients with DV infection and from 19 patients with other febrile illnesses were prospectively analyzed for viral load and for levels of NS1 and complement-activation products. Blood and pleural fluids from 9 patients with DSS were also analyzed.
Soluble NS1 activated complement to completion, and activation was enhanced by polyclonal and monoclonal antibodies against NS1. Complement was also activated by cell-associated NS1 in the presence of specific antibodies. Plasma levels of NS1 and terminal SC5b-9 complexes correlated with disease severity. Large amounts of NS1, complement anaphylatoxin C5a, and the terminal complement complex SC5b-9 were present in pleural fluids from patients with DSS.
Complement activation mediated by NS1 leads to local and systemic generation of anaphylatoxins and SC5b-9, which may contribute to the pathogenesis of the vascular leakage that occurs in patients with DHF/DSS.
血管渗漏和休克是登革出血热（DHF）和登革休克综合征（DSS）患者死亡的主要原因。30年前，补体激活被认为是一个关键的潜在事件，但补体激活的原因仍不清楚。
检测登革病毒（DV）主要非结构蛋白NS1以其膜结合形式和可溶性形式激活人补体的能力。前瞻性分析了163例DV感染患者和19例其他发热性疾病患者的血浆样本中的病毒载量、NS1水平和补体激活产物水平。还分析了9例DSS患者的血液和胸水。
可溶性NS1可使补体完全激活，针对NS1的多克隆抗体和单克隆抗体可增强激活作用。在特异性抗体存在的情况下，细胞相关NS1也可激活补体。NS1血浆水平和终末SC5b-9复合物与疾病严重程度相关。DSS患者胸水中存在大量NS1、补体过敏毒素C5a和终末补体复合物SC5b-9。
NS1介导的补体激活导致过敏毒素和SC5b-9在局部和全身产生，这可能有助于DHF/DSS患者发生血管渗漏的发病机制。
