Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients
Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients
复制标题
DOI：
10.1038/7422
复制
发表时间：
1999-04-01
期刊：
影响因子：
82.9
通讯作者：
Georges, AJ
中科院分区：
文献类型：
--
作者：
Baize, S;Leroy, EM;Georges, AJ
埃博拉病毒对人类的致病性很强。它会引起急性出血热，导致约70%的患者死亡。我们比较了死于埃博拉病毒疾病的患者和那些在1996年加蓬两次大规模疫情中幸存下来的患者的免疫反应。在幸存者中，早期和增加的主要针对核蛋白和40 kDa病毒蛋白的免疫球蛋白水平，随之而来的是循环病毒抗原的清除和细胞毒性T细胞的激活，这表现为外周血单核细胞中Fast、穿孔素、CD28和伽马干扰素mRNA的上调。相比之下，致命性感染的特点是体液反应受损，缺乏特异性免疫球蛋白G，几乎检测不到免疫球蛋白M。死亡前几天，T细胞相关的mRNA(包括CD3和CD8)消失，表明T细胞的早期激活，由外周血单个核细胞中的mRNA模式和血浆中相当数量的干扰素释放来指示。血白细胞DNA片段化和血浆中41/7核基质蛋白的释放表明，在生命的最后5天，大量的血管内细胞凋亡持续进行。因此，埃博拉病毒感染的早期事件决定了对病毒复制和恢复或灾难性疾病和死亡的控制。
Ebola virus is very pathogenic in humans. It induces an acute hemorrhagic fever that leads to death in about 70% of patients'. We compared the immune responses of patients who died from Ebola virus disease with those who survived during two large outbreaks in 1996 in Gabon. In survivors, early and increasing levels of IgG, directed mainly against the nucleoprotein and the 40-kDa viral protein, were followed by clearance of circulating viral antigen and activation of cytotoxic T cells, which was indicated by the upregulation of Fast, perforin, CD28 and gamma interferon mRNA in peripheral blood mononuclear cells. In contrast, fatal infection was characterized by impaired humoral responses, with absent specific IgG and barely detectable IgM. Early activation of T cells, indicated by mRNA patterns in peripheral blood mononuclear cells and considerable release of gamma interferon in plasma, was followed in the days preceding death by the disappearance of T cell-related mRNA (including CD3 and CD8). DNA fragmentation in blood leukocytes and release of 41/7 nuclear matrix protein in plasma indicated that massive intravascular apoptosis proceeded relentlessly during the last 5 days of life. Thus, events very early in Ebola virus infection determine the control of viral replication and recovery or catastrophic illness and death.