Marburg virus Angola infection of rhesus macaques: Pathogenesis and treatment with recombinant nematode anticoagulant protein c2

Thomas W. Geisbert, Kathleen M. Daddario-DiCaprio, Joan B. Geisbert, Howard A. Young, Pierre Formenty, Elizabeth A. Fritz, Tom Larsen, Lisa E. Hensley

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91 Scopus citations

Abstract

Background. The procoagulant tissue factor (TF) is thought to play a role in the coagulation disorders that characterize filoviral infections. In this study, we evaluated the pathogenesis of lethal infection with the Angola strain of Marburg virus (MARV-Ang) in rhesus macaques and tested the efficacy of recombinant nematode anticoagulant protein c2 (rNAPc2), an inhibitor of TF/factor VIIa, as a potential treatment. Methods. Twelve rhesus macaques were challenged with a high dose (1000 pfu) of MARV-Ang. Six macaques were treated with rNAPc2, and 6 macaques served as control animals. Results. All 6 control animals succumbed to MARV-Ang challenge by day 8 (mean, 7.3 days), whereas 5 of 6 rNAPc2-treated animals died on day 9 and 1 rNAPc2-treated animal survived. The disease course for MARV-Ang infection appeared to progress more rapidly in rhesus macaques than has been previously reported for other strains of MARV. In contrast to Ebola virus (EBOV) infection in macaques, up-regulation of TF was not as striking, and deposition of fibrin was a less prominent pathologic feature of disease in these animals. Conclusions. These data show that the pathogenicity of MARV-Ang infection appears to be consistent with the apparent increased human virulence attributed to this strain. The apparent reduced efficacy of rNAPc2 against MARV-Ang infection, compared with its efficacy against EBOV infection, appears to be associated with differences in TF induction and fibrin deposition.

Original languageEnglish (US)
Pages (from-to)S372-S381
JournalJournal of Infectious Diseases
Volume196
Issue numberSUPPL. 2
DOIs
StatePublished - Nov 15 2007

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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    Geisbert, T. W., Daddario-DiCaprio, K. M., Geisbert, J. B., Young, H. A., Formenty, P., Fritz, E. A., Larsen, T., & Hensley, L. E. (2007). Marburg virus Angola infection of rhesus macaques: Pathogenesis and treatment with recombinant nematode anticoagulant protein c2. Journal of Infectious Diseases, 196(SUPPL. 2), S372-S381. https://doi.org/10.1086/520608