Marburg virus Angola infection of rhesus macaques

Pathogenesis and treatment with recombinant nematode anticoagulant protein c2

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

Research output: Contribution to journalArticle

87 Citations (Scopus)

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)
JournalJournal of Infectious Diseases
Volume196
Issue numberSUPPL. 2
DOIs
StatePublished - Nov 15 2007
Externally publishedYes

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Marburgvirus
Angola
Virus Diseases
Macaca mulatta
Thromboplastin
Ebola Hemorrhagic Fever
Macaca
Infection
Fibrin
Virulence
Factor VIIa
Animal Diseases
Up-Regulation
Ancylostoma caninum anti-coagulant protein C2

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Marburg virus Angola infection of rhesus macaques : Pathogenesis and treatment with recombinant nematode anticoagulant protein c2. / Geisbert, Thomas; Daddario-DiCaprio, Kathleen M.; Geisbert, Joan B.; Young, Howard A.; Formenty, Pierre; Fritz, Elizabeth A.; Larsen, Tom; Hensley, Lisa E.

In: Journal of Infectious Diseases, Vol. 196, No. SUPPL. 2, 15.11.2007.

Research output: Contribution to journalArticle

Geisbert, T, Daddario-DiCaprio, KM, Geisbert, JB, Young, HA, Formenty, P, Fritz, EA, Larsen, T & Hensley, LE 2007, 'Marburg virus Angola infection of rhesus macaques: Pathogenesis and treatment with recombinant nematode anticoagulant protein c2', Journal of Infectious Diseases, vol. 196, no. SUPPL. 2. https://doi.org/10.1086/520608
Geisbert, Thomas ; Daddario-DiCaprio, Kathleen M. ; Geisbert, Joan B. ; Young, Howard A. ; Formenty, Pierre ; Fritz, Elizabeth A. ; Larsen, Tom ; Hensley, Lisa E. / Marburg virus Angola infection of rhesus macaques : Pathogenesis and treatment with recombinant nematode anticoagulant protein c2. In: Journal of Infectious Diseases. 2007 ; Vol. 196, No. SUPPL. 2.
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