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

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.

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@article{Geisbert2007MarburgVA, title={Marburg virus Angola infection of rhesus macaques: pathogenesis and treatment with recombinant nematode anticoagulant protein c2.}, author={Thomas W. Geisbert and Kathleen M. Daddario-DiCaprio and Thomas W Geisbert and Howard A Young and Pierre B H Formenty and Elizabeth A. Fritz and Tom Larsen and Lisa E. Hensley}, journal={The Journal of infectious diseases}, year={2007}, volume={196 Suppl 2}, pages={S372-81} }