期刊
JOURNAL OF INFECTIOUS DISEASES
卷 213, 期 5, 页码 703-711出版社
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jiv538
关键词
Ebola virus disease; animal model; viral hemorrhagic fever; humanized mice; cytokine profile; virus pathogenesis
资金
- Centers for Disease Control and Prevention (CDC)
- CDC Research Participation Program
- National Institutes of Health Loan Repayment Program
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.
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