Martina Byron E E
Department of Viroscience, Rotterdam, The Netherlands.
Sci Prog. 2014;97(Pt 3):197-214. doi: 10.3184/003685014X14049173153889.
Dengue viruses cause mild disease in the majority of infected individuals. In most cases, the disease is characterised by fever, headache, pain behind the eyes, muscle ache, joint pains, vomiting and diarrhoea. In a low percentage of patients, bleeding and loss of plasma (haemorrhage and plasma leakage) may occur. The hyper-permeability syndrome results in plasma leakage and, if the compensatory mechanisms of the body fail to control the plasma leakage or if medical intervention is late, shock may set in. Profound shock will subsequently lead to acidic blood (metabolic acidosis) and development of disseminated intravascular coagulation (DIC). During DIC multiple micro thromboses occur, leading to organ failure. The mechanisms governing pathogenesis of these forms of severe disease are not clear. High amounts of virus in the blood are believed to cause vascular fragility which, together with infection of endothelial cells and high levels of cytokines and other soluble mediators, may result in bleeding. In the absence of a correlation between the amount of virus in the blood and disease severity, it is likely that response to infection is an important cause of disease. The aberrant immune response to infection is believed to result in a cytokine storm, defined as an imbalance between cytokines driving an inflammation (pro-inflammatory) and those silencing an inflammation (anti-inflammatory). Several lines of evidence indicate that displacement of viral genotype and host genetic background are key factors driving the production of a cytokine storm. Several cytokines are known to induce apoptosis, a form of cell suicide (cause of haemorrhage), and/or affect adherens junctions (cause permeability) in vitro. Whether these cytokines may have such effects in vivo remains to be established.
登革病毒在大多数感染者中引起轻度疾病。在大多数情况下，该疾病的特征为发热、头痛、眼后疼痛、肌肉酸痛、关节疼痛、呕吐和腹泻。在低比例患者中，可能会出现出血和血浆流失（出血和血浆渗漏）。高通透性综合征会导致血浆渗漏，如果身体的代偿机制无法控制血浆渗漏，或者医疗干预不及时，可能会发生休克。严重休克随后会导致血液酸化（代谢性酸中毒）和弥散性血管内凝血（DIC）的发展。在DIC期间，会出现多个微血栓，导致器官衰竭。这些严重疾病形式的发病机制尚不清楚。血液中大量病毒被认为会导致血管脆弱，这与内皮细胞感染以及高水平的细胞因子和其他可溶性介质一起，可能导致出血。由于血液中病毒量与疾病严重程度之间缺乏相关性，对感染的反应很可能是疾病的一个重要原因。对感染的异常免疫反应被认为会导致细胞因子风暴，即驱动炎症的细胞因子（促炎）与抑制炎症的细胞因子（抗炎）之间的失衡。几条证据表明，病毒基因型的置换和宿主遗传背景是驱动细胞因子风暴产生的关键因素。已知几种细胞因子在体外可诱导细胞凋亡，一种细胞自杀形式（出血原因），和/或影响黏附连接（导致通透性）。这些细胞因子在体内是否具有此类作用仍有待确定。
