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

Nature Medicine volume 5, pages 423–426 (1999)Cite this article

Abstract

Ebola virus is very pathogenic in humans. It induces an acute hemorrhagic fever that leads to death in about 70% of patients1. 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 FasL, 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.

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Figure 1: Circulating Ebola antigen levels and humoral responses in Ebola-infected patients.
Figure 2: Analysis of T-cell responses in Ebola-infected patients.
Figure 3: Detection of apoptosis in fatalities.

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Acknowledgements

We are grateful to C. Tevi-Benissan and P. Tshipamba for their assistance on fieldwork, and A. Pendy, B. Pambo and P. Obiang for access to patient specimens. We also thank V.E. Volchkov, P.E. Rollin and T.G. Ksiazek for providing Ebola-specific reagents and for their assistance with western blot analysis and IgM detection. S.B. is supported by a grant from the Ministère de la Recherche et de l'Enseignement Supérieur (France). CIRMF is supported by the state of Gabon, ELF-Gabon and the Ministère de la Coopération Française.

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Author notes

  1. S.B. and E.M.L. contributed equally to this work

Authors and Affiliations

  1. Centre International de Recherches Médicales de Franceville, B.P. 769, Franceville, Gabon

    Sylvain Baize, Eric M. Leroy, M.-C. Georges-Courbot, Joseph Lansoud-Soukate & Alain J. Georges

  2. Centre d'Immunologie et de Biologie Parasitaire, INSERM U 167, Institut Pasteur de Lille, 1 rue du Professeur Calmette , Lille, 59019, France

    Sylvain Baize & Monique Capron

  3. Laboratoire Central d'Immunologie Cellulaire et Tissulaire, CNRS U 625, hôpital de la Pitié-Salpétrière, Paris,, France

    Patrice Debré

  4. Fondation Marcel Mérieux, 17 rue Bourgelat, Lyon, 69002, France

    Susan P. Fisher-Hoch

  5. Pasteur/Mérieux/Connaught, 1541 avenue Marcel Mérieux, Marcy l'Etoile , 69260, France

    Joseph B. McCormick

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  1. Sylvain Baize
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Correspondence to Sylvain Baize or Eric M. Leroy.

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Baize, S., Leroy, E., Georges-Courbot, MC. et al. Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients. Nat Med 5, 423–426 (1999). https://doi.org/10.1038/7422

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