Host genetic diversity enables Ebola hemorrhagic fever pathogenesis and resistance

被引：207

作者：

Rasmussen, Angela L. ^{[1
]}

Okumura, Atsushi ^{[1
,4
]}

Ferris, Martin T. ^{[2
]}

Green, Richard ^{[1
]}

Feldmann, Friederike ^{[3
]}

Kelly, Sara M. ^{[1
]}

Scott, Dana P. ^{[3
]}

Safronetz, David ^{[4
]}

Haddock, Elaine ^{[4
]}

LaCasse, Rachel ^{[3
]}

Thomas, Matthew J. ^{[1
]}

Sova, Pavel ^{[1
]}

Carter, Victoria S. ^{[1
]}

Weiss, Jeffrey M. ^{[1
]}

Miller, Darla R. ^{[2
]}

Shaw, Ginger D. ^{[2
]}

Korth, Marcus J. ^{[1
]}

Heise, Mark T. ^{[2
,5
]}

Baric, Ralph S. ^{[5
]}

de Villena, Fernando Pardo-Manuel ^{[2
]}

Fedlmann, Heinz ^{[4
]}

Katze, Michael G. ^{[1
,6
]}

机构：

[1] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA

[2] Univ N Carolina, Dept Genet, Chapel Hill, NC USA

[3] NIAID, Rocky Mt Vet Branch, NIH, Rocky Mt Labs, Hamilton, MT USA

[4] NIAID, Virol Lab, NIH, Rocky Mt Labs, Hamilton, MT USA

[5] Univ N Carolina, Dept Microbiol & Immunol, Chapel Hill, NC USA

[6] Washington Natl Primate Res Ctr, Seattle, WA USA

来源：

SCIENCE | 2014年 / 346卷 / 6212期

基金：

美国国家卫生研究院;

关键词：

VIRUS INFECTION; GUINEA-PIGS; COAGULATION; OUTBREAK; MAP;

D O I：

10.1126/science.1259595

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Existing mouse models of lethal Ebola virus infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever, neither delayed blood coagulation and disseminated intravascular coagulation nor death fromshock, thus restricting pathogenesis studies to nonhuman primates. Here we show that mice from the Collaborative Cross panel of recombinant inbred mice exhibit distinct disease phenotypes after mouse-adapted Ebola virus infection. Phenotypes range from complete resistance to lethal disease to severe hemorrhagic fever characterized by prolonged coagulation times and 100% mortality. Inflammatory signaling was associated with vascular permeability and endothelial activation, and resistance to lethal infection arose by induction of lymphocyte differentiation and cellular adhesion, probably mediated by the susceptibility allele Tek. These data indicate that genetic background determines susceptibility to Ebola hemorrhagic fever.

引用

页码：987 / 991

页数：5

共 27 条

[1] Coagulation, Protease-Activated Receptors, and Viral Myocarditis [J].

Antoniak, Silvio ;

Mackman, Nigel .

JOURNAL OF CARDIOVASCULAR TRANSLATIONAL RESEARCH, 2014, 7 (02) :203-211

[2] Emergence of Zaire Ebola Virus Disease in Guinea [J].

Baize, Sylvain ;

Pannetier, Delphine ;

Oestereich, Lisa ;

Rieger, Toni ;

Koivogui, Lamine ;

Magassouba, N'Faly ;

Soropogui, Barre ;

Sow, Mamadou Saliou ;

Keita, Sakoba ;

De Clerck, Hilde ;

Tiffany, Amanda ;

Dominguez, Gemma ;

Loua, Mathieu ;

Traore, Alexis ;

Kolie, Moussa ;

Malano, Emmanuel Roland ;

Heleze, Emmanuel ;

Bocquin, Anne ;

Mely, Stephane ;

Raoul, Herve ;

Caro, Valerie ;

Cadar, Daniel ;

Gabriel, Martin ;

Pahlmann, Meike ;

Tappe, Dennis ;

Schmidt-Chanasit, Jonas ;

Impouma, Benido ;

Diallo, Abdoul Karim ;

Formenty, Pierre ;

Van Herp, Michel ;

Guenther, Stephan .

NEW ENGLAND JOURNAL OF MEDICINE, 2014, 371 (15) :1418-1425

[3] Expression Quantitative Trait Loci for Extreme Host Response to Influenza A in Pre-Collaborative Cross Mice [J].

Bottomly, Daniel ;

Ferris, Martin T. ;

Aicher, Lauri D. ;

Rosenzweig, Elizabeth ;

Whitmore, Alan ;

Aylor, David L. ;

Haagmans, Bart L. ;

Gralinski, Lisa E. ;

Bradel-Tretheway, Birgit G. ;

Bryan, Janine T. ;

Threadgill, David W. ;

de Villena, Fernando Pardo-Manuel ;

Baric, Ralph S. ;

Katze, Michael G. ;

Heise, Mark ;

McWeeney, Shannon K. .

G3-GENES GENOMES GENETICS, 2012, 2 (02) :213-221

[4] 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

[5] High-resolution physical and transcript map of the locus for venous malformations with glomus cells (VMGLOM) on chromosome 1p21-p22 [J].

Brouillard, P ;

Olsen, BR ;

Vikkula, M .

GENOMICS, 2000, 67 (01) :96-101

[6] Pathogenesis of experimental Ebola virus infection in guinea pigs [J].

Connolly, BM ;

Steele, KE ;

Davis, KJ ;

Geisbert, TW ;

Kell, WM ;

Jaax, NK ;

Jahrling, PB .

JOURNAL OF INFECTIOUS DISEASES, 1999, 179 :S203-S217

[7]

Dixon MG, 2014, MMWR-MORBID MORTAL W, V63, P548

[8] Molecular determinants of Ebola virus virulence in mice [J].

Ebihara, Hideki ;

Takada, Ayato ;

Kobasa, Darwyn ;

Jones, Steven ;

Neumann, Gabriele ;

Theriault, Steven ;

Bray, Mike ;

Feldmann, Heinz ;

Kawaoka, Yoshihiro .

PLOS PATHOGENS, 2006, 2 (07) :705-711

[9] A Syrian Golden Hamster Model Recapitulating Ebola Hemorrhagic Fever [J].

Ebihara, Hideki ;

Zivcec, Marko ;

Gardner, Donald ;

Falzarano, Darryl ;

LaCasse, Rachel ;

Rosenke, Rebecca ;

Long, Dan ;

Haddock, Elaine ;

Fischer, Elizabeth ;

Kawaoka, Yoshihiro ;

Feldmann, Heinz .

JOURNAL OF INFECTIOUS DISEASES, 2013, 207 (02) :306-318

[10] Host Response Dynamics Following Lethal Infection of Rhesus Macaques With Zaire ebolavirus [J].

Ebihara, Hideki ;

Rockx, Barry ;

Marzi, Andrea ;

Feldmann, Friederike ;

Haddock, Elaine ;

Brining, Douglas ;

LaCasse, Rachel A. ;

Gardner, Don ;

Feldmann, Heinz .

JOURNAL OF INFECTIOUS DISEASES, 2011, 204 :S991-S999

← 1 2 3 →