A Syrian Golden Hamster Model Recapitulating Ebola Hemorrhagic Fever

被引:89
作者
Ebihara, Hideki [1 ,2 ,3 ]
Zivcec, Marko [1 ,2 ,4 ]
Gardner, Donald [5 ]
Falzarano, Darryl [1 ,2 ,4 ]
LaCasse, Rachel [5 ]
Rosenke, Rebecca [5 ]
Long, Dan [5 ]
Haddock, Elaine [1 ]
Fischer, Elizabeth [6 ]
Kawaoka, Yoshihiro [3 ,7 ,8 ]
Feldmann, Heinz [1 ,2 ,4 ]
机构
[1] NIAID, Virol Lab, Div Intramural Res, Natl Inst Hlth NID,RML, Hamilton, MT 59840 USA
[2] Publ Hlth Agcy Canada, Natl Microbiol Lab, Winnipeg, MB, Canada
[3] Univ Tokyo, Inst Med Sci, Int Res Ctr Infect Dis, Dept Special Pathogens, Tokyo 1138654, Japan
[4] Univ Manitoba, Dept Med Microbiol, Winnipeg, MB, Canada
[5] NIAID, Rocky Mt Vet Branch, NIH, Hamilton, MT 59840 USA
[6] NIAID, RML Res Technol Sect, Div Intramural Res, NIH, Hamilton, MT 59840 USA
[7] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Virol, Tokyo 1138654, Japan
[8] Univ Wisconsin, Sch Vet Med, Dept Pathobiol Sci, Madison, WI 53706 USA
关键词
ebolavirus; Ebola hemorrhagic fever; animal model; pathogenesis; coagulopathy; NECROSIS-FACTOR-ALPHA; VIRUS-INFECTION; PROTEIN-C; POSTEXPOSURE TREATMENT; IMMUNE-RESPONSES; LETHAL INFECTION; MOUSE MODEL; GUINEA-PIGS; PATHOGENESIS; COAGULATION;
D O I
10.1093/infdis/jis626
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Ebola hemorrhagic fever (EHF) is a severe viral infection for which no effective treatment or vaccine is currently available. While the nonhuman primate (NHP) model is used for final evaluation of experimental vaccines and therapeutic efficacy, rodent models have been widely used in ebolavirus research because of their convenience. However, the validity of rodent models has been questioned given their low predictive value for efficacy testing of vaccines and therapeutics, a result of the inconsistent manifestation of coagulopathy seen in EHF. Here, we describe a lethal Syrian hamster model of EHF using mouse-adapted Ebola virus. Infected hamsters displayed most clinical hallmarks of EHF, including severe coagulopathy and uncontrolled host immune responses. Thus, the hamster seems to be superior to the existing rodent models, offering a better tool for understanding the critical processes in pathogenesis and providing a new model for evaluating prophylactic and postexposure interventions prior to testing in NHPs.
引用
收藏
页码:306 / 318
页数:13
相关论文
共 50 条
[1]   The IFN-inducible GTPase LRG47 (Irgm1) negatively regulates TLR4-triggered proinflammatory cytokine production and prevents endotoxemia [J].
Bafica, Andre ;
Feng, Carl G. ;
Santiago, Helton C. ;
Aliberti, Julio ;
Cheever, Allen ;
Thomas, Karen E. ;
Taylor, Gregory A. ;
Vogel, Stefanie N. ;
Sher, Alan .
JOURNAL OF IMMUNOLOGY, 2007, 179 (08) :5514-5522
[2]   Defective humoral responses and extensive intravascular apoptosis are associated with fatal outcome in Ebola virus-infected patients [J].
Baize, S ;
Leroy, EM ;
Georges-Courbot, MC ;
Capron, M ;
Lansoud-Soukate, J ;
Debré, P ;
Fisher-Hoch, SP ;
McCormick, JB ;
McCormick, JB ;
Georges, AJ .
NATURE MEDICINE, 1999, 5 (04) :423-426
[3]   Inflammatory responses in Ebola virus-infected patients [J].
Baize, S ;
Leroy, EM ;
Georges, AJ ;
Georges-Courbot, MC ;
Capron, M ;
Bedjabaga, I ;
Lansoud-Soukate, J ;
Mavoungou, E .
CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 2002, 128 (01) :163-168
[4]   The Ebola virus VP35 protein functions as a type IIFN antagonist [J].
Basler, CF ;
Wang, XY ;
Mühlberger, E ;
Volchkov, V ;
Paragas, J ;
Klenk, HD ;
Garcia-Sastre, A ;
Palese, P .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (22) :12289-12294
[5]   Evasion of Interferon Responses by Ebola and Marburg Viruses [J].
Basler, Christopher F. ;
Amarasinghe, Gaya K. .
JOURNAL OF INTERFERON AND CYTOKINE RESEARCH, 2009, 29 (09) :511-520
[6]   Disease modeling for Ebola and Marburg viruses [J].
Bente, Dennis ;
Gren, Jason ;
Strong, James E. ;
Feldmann, Heinz .
DISEASE MODELS & MECHANISMS, 2009, 2 (1-2) :12-17
[7]   Mechanisms and Consequences of Ebolavirus-Induced Lymphocyte Apoptosis [J].
Bradfute, Steven B. ;
Swanson, Paul E. ;
Smith, Mark A. ;
Watanabe, Eizo ;
McDunn, Jonathan E. ;
Hotchkiss, Richard S. ;
Bavari, Sina .
JOURNAL OF IMMUNOLOGY, 2010, 184 (01) :327-335
[8]   Ebola hemorrhagic fever and septic shock [J].
Bray, M ;
Mahanty, S .
JOURNAL OF INFECTIOUS DISEASES, 2003, 188 (11) :1613-1617
[9]   A mouse model for evaluation of prophylaxis and therapy of Ebola hemorrhagic fever [J].
Bray, M ;
Davis, K ;
Geisbert, T ;
Schmaljohn, C ;
Huggins, J .
JOURNAL OF INFECTIOUS DISEASES, 1998, 178 (03) :651-661
[10]   Haematological, biochemical and coagulation changes in mice, guinea-pigs and monkeys infected with a mouse-adapted variant of Ebola Zaire virus [J].
Bray, M ;
Hatfill, S ;
Hensley, L ;
Huggins, JW .
JOURNAL OF COMPARATIVE PATHOLOGY, 2001, 125 (04) :243-253