title: Humanized Mouse Model of Ebola Virus Disease Mimics the Immune Responses in Human Disease.
abstract: 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.
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: Brian H
authors.initials: BH
authors.lastname: Bird
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: Jessica R
authors.initials: JR
authors.lastname: Spengler
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: Ayan K
authors.initials: AK
authors.lastname: Chakrabarti
authors.affiliation: Biotechnology Core Facility.
authors.forename: Marina L
authors.initials: ML
authors.lastname: Khristova
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: Tara K
authors.initials: TK
authors.lastname: Sealy
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: JoAnn D
authors.initials: JD
authors.lastname: Coleman-McCray
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: Brock E
authors.initials: BE
authors.lastname: Martin
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Dodd
authors.affiliation: Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Cynthia S
authors.initials: CS
authors.lastname: Goldsmith
authors.affiliation: Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Jeanine
authors.initials: J
authors.lastname: Sanders
authors.affiliation: Infectious Diseases Pathology Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia.
authors.forename: Sherif R
authors.initials: SR
authors.lastname: Zaki
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: Stuart T
authors.initials: ST
authors.lastname: Nichol
authors.affiliation: Viral Special Pathogens Branch.
authors.forename: Christina F
authors.initials: CF
authors.lastname: Spiropoulou
mesh_terms: D000818:Animals; D001921:Brain / Q000821:virology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D029043:Ebolavirus / Q000502:physiology*; D005786:Gene Expression Regulation / Q000276:immunology*; D019142:Hemorrhagic Fever, Ebola / Q000276:immunology* / Q000652:urine / Q000821:virology; D006801:Humans; D007668:Kidney / Q000821:virology; D008099:Liver / Q000821:virology; D008168:Lung / Q000821:virology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D012367:RNA, Viral / Q000302:isolation & purification; D013154:Spleen / Q000821:virology; D013737:Testis / Q000821:virology; D014779:Virus Replication
chemical_list: D016207:Cytokines; D012367:RNA, Viral
keywords: Ebola virus disease; animal model; cytokine profile; humanized mice; viral hemorrhagic fever; virus pathogenesis