Marburg virus Angola infection of rhesus macaques: pathogenesis and treatment with recombinant nematode anticoagulant protein c2
Autor: | Lisa E. Hensley, Tom Larsen, Elizabeth A. Fritz, Kathleen M. Daddario-DiCaprio, Pierre Formenty, Thomas W. Geisbert, Joan B. Geisbert, Howard A. Young |
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Rok vydání: | 2007 |
Předmět: |
Filoviridae
Supplement Articles medicine.disease_cause Virus Pathogenesis 03 medical and health sciences Marburg virus disease medicine Immunology and Allergy Animals Marburg Virus Disease Mononegavirales Prophylaxis and Therapy 030304 developmental biology 0303 health sciences Ebola virus biology 030306 microbiology Recombinant Nematode Anticoagulant Protein c2 Primate Diseases Helminth Proteins Marburgvirus biology.organism_classification Virology Macaca mulatta Recombinant Proteins 3. Good health Infectious Diseases Angola |
Zdroj: | The Journal of Infectious Diseases |
ISSN: | 0022-1899 |
Popis: | 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 MARVAng 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. |
Databáze: | OpenAIRE |
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