Lessons from the survivors of Ebola infection

Abstract

Ebola virus, which causes viral hemorrhagic fever, is one of humankind’s most pathogenic infections, and has a mortality rate of 60–80%. Against such odds, do host or viral factors determine survival? In a study of two clusters in Gabon in 1996, Baize et al. 1 Baize S. et al. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat. Med. 1999; 5: 423-426 Crossref PubMed Scopus (445) Google Scholar measured viral load, antibody responses, mRNA for T-cell-activation markers, T-cell apoptosis and circulating interferon γ (IFN-γ) levels in Ebola patients. Clear distinctions between individuals were evident, with survivors developing specific immunoglobulin G within five days of illness and cytotoxic T lymphocyte (CTL)-responses shortly afterwards. Those who did not survive, by contrast, had a poor immunoglobulin response, rising IFN-γ levels and dramatic T-cell apoptosis (consistent with the lymphoreticular damage characteristic of such patients at post mortem). Viral loads differed little between groups, suggesting that the early host response was critical in determining outcome. Specific antibodies were directed against a viral nucleoprotein and several smaller proteins rather than against transmembrane structures. Thus early T-cell responses determined survival, as has been found in rodent models of Ebola infection; such responses direct the production of appropriate antibodies. This information should help direct Ebola vaccine development, and raises questions as to how clinicians might enhance T-cell response times.