Aerosol Exposure to the Angola Strain of Marburg Virus Causes Lethal Viral Hemorrhagic Fever in Cynomolgus Macaques

被引:66
作者
Alves, D. A. [2 ]
Glynn, A. R. [2 ]
Steele, K. E. [2 ]
Lackemeyer, M. G. [2 ]
Garza, N. L. [2 ]
Buck, J. G. [2 ]
Mech, C. [2 ]
Reed, D. S. [1 ]
机构
[1] Univ Pittsburgh, Ctr Vaccine Res, Pittsburgh, PA 15261 USA
[2] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA
关键词
Marburg virus; aerosol; nonhuman primate; animal model; HIGH ENDOTHELIAL VENULES; EBOLA-VIRUS; NONHUMAN-PRIMATES; DENDRITIC CELLS; RHESUS-MONKEYS; RESTON-VIRUS; LYMPH-NODES; MOUSE MODEL; GUINEA-PIGS; INFECTION;
D O I
10.1177/0300985810378597
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
Cynomolgus macaques were exposed to the Angola strain of Lake Victoria Marburg virus (MARV) by aerosol to examine disease course and lethality. Macaques became febrile 4 to 7 days postexposure; the peak febrile response was delayed 1 to 2 days in animals that received a lower dose; viremia coincided with the onset of fever. All 6 macaques succumbed to the infection, with the 3 macaques in the low-dose group becoming moribund on day 9, a day later than the macaques in the high-dose group. Gross pathologic lesions included maculopapular cutaneous rash; pulmonary congestion and edema; pericardial effusion; enlarged, congested, and/or hemorrhagic lymphoid tissues; enlarged friable fatty liver; and pyloric and duodenal congestion and/or hemorrhage. Fibrinous interstitial pneumonia was the most consistent pulmonary change. Lymphocytolysis and lymphoid depletion, as confirmed by TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling), were observed in the mediastinal lymph nodes and spleen. MARV antigen was detected in the lungs, mediastinal lymph nodes, spleen, and liver of all animals examined. In infected macaques, nuclear expression of interleukin-33 was lost in pulmonary arteriolar and mediastinal lymph node high endothelial venule endothelial cells; interleukin-33-positive fibroblastic reticular cells in the mediastinal lymph node were consistently negative for MARV antigen. These macaques exhibited a number of features similar to those of human filovirus infections; as such, this model of aerosolized MARV-Angola might be useful in developing medical countermeasures under the Animal Rule.
引用
收藏
页码:831 / 851
页数:21
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