Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease

Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with h...

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Bibliographic Details
Published in:The Journal of infectious diseases 2016-03, Vol.213 (5), p.703-711
Main Authors: Bird, Brian H., Spengler, Jessica R., Chakrabarti, Ayan K., Khristova, Marina L., Sealy, Tara K., Coleman-McCray, JoAnn D., Martin, Brock E., Dodd, Kimberly A., Goldsmith, Cynthia S., Sanders, Jeanine, Zaki, Sherif R., Nichol, Stuart T., Spiropoulou, Christina F.
Format: Article
Language:English
Subjects:
Animals
Brain - virology
Cytokines - genetics
Cytokines - metabolism
Ebola virus
Ebolavirus
Ebolavirus - physiology
Gene Expression Regulation - immunology
Hemorrhagic Fever, Ebola - immunology
Hemorrhagic Fever, Ebola - urine
Hemorrhagic Fever, Ebola - virology
Humans
Kidney - virology
Liver - virology
Lung - virology
Major and Brief Reports
Male
Mice
Mice, Transgenic
RNA, Viral - isolation & purification
Spleen - virology
Testis - virology
Virus Replication
VIRUSES
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Summary:Animal models recapitulating human Ebola virus disease (EVD) are critical for insights into virus pathogenesis. Ebola virus (EBOV) isolates derived directly from human specimens do not, without adaptation, cause disease in immunocompetent adult rodents. Here, we describe EVD in mice engrafted with human immune cells (hu-BLT). hu-BLT mice developed EVD following wild-type EBOV infection. Infection with high-dose EBOV resulted in rapid, lethal EVD with high viral loads, alterations in key human antiviral immune cytokines and chemokines, and severe histopathologic findings similar to those shown in the limited human postmortem data available. A dose- and donor-dependent clinical course was observed in hu-BLT mice infected with lower doses of either Mayinga (1976) or Makona (2014) isolates derived from human EBOV cases. Engraftment of the human cellular immune system appeared to be essential for the observed virulence, as nonengrafted mice did not support productive EBOV replication or develop lethal disease. hu-BLT mice offer a unique model for investigating the human immune response in EVD and an alternative animal model for EVD pathogenesis studies and therapeutic screening.
ISSN:0022-1899
1537-6613
DOI:10.1093/infdis/jiv538