Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients

Ebola virus is very pathogenic in humans. It induces an acute hemorrhagic f ever 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 surv ived during two large outbreaks in 1996 in Gabon. In survivors, early and i ncreasing levels of IgG, directed mainly against the nucleoprotein and the 40-kDa viral protein, were followed by clearance of circulating viral antig en and activation of cytotoxic T cells, which was indicated by the upregula tion of Fast, perforin, CD28 and gamma interferon mRNA in peripheral blood mononuclear cells. In contrast, fatal infection was characterized by impair ed humoral responses, with absent specific IgG and barely detectable IgM. E arly activation of T cells, indicated by mRNA patterns in peripheral blood mononuclear cells and considerable release of gamma interferon in plasma, w as followed in the days preceding death by the disappearance of T cell-rela ted mRNA (including CD3 and CD8). DNA fragmentation in blood leukocytes and release of 41/7 nuclear matrix protein in plasma indicated that massive in travascular 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.