Marburg virus Angola infection of rhesus macaques: pathogenesis and treatment with recombinant nematode anticoagulant protein c2.
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.
Geisbert
Thomas W
TW
Integrated Research Facility at Fort Detrick, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD, USA. tgeisbert@bu.edu
Daddario-DiCaprio
Kathleen M
KM
Geisbert
Joan B
JB
Young
Howard A
HA
Formenty
Pierre
P
Fritz
Elizabeth A
EA
Larsen
Tom
T
Hensley
Lisa E
LE
D000810:Angola / Q000453:epidemiology; D000818:Animals; D015801:Helminth Proteins / Q000627:therapeutic use*; D008253:Macaca mulatta; D008379:Marburg Virus Disease / Q000188:drug therapy* / Q000453:epidemiology*; D029024:Marburgvirus / Q000472:pathogenicity*; D018419:Primate Diseases / Q000188:drug therapy / Q000453:epidemiology; D011994:Recombinant Proteins / Q000627:therapeutic use
D015801:Helminth Proteins; D011994:Recombinant Proteins; C400226:anti-coagulant protein C2, Ancylostoma caninum