title: Modeling the Disease Course of Zaire ebolavirus Infection in the Outbred Guinea Pig.
abstract: BACKGROUND
  Rodent models that accurately reflect human filovirus infection are needed as early screens for medical countermeasures. Prior work in rodents with the Zaire species of Ebola virus (ZEBOV) primarily used inbred mice and guinea pigs to model disease. However, these inbred species do not show some of the important features of primate ZEBOV infection, most notably, coagulation abnormalities.
  
  
  METHODS
  Thirty-six outbred guinea pigs were infected with guinea pig-adapted ZEBOV and examined sequentially over an 8-day period to investigate the pathologic events that lead to death.
  
  
  RESULTS
  Features of disease in ZEBOV-infected outbred guinea pigs were largely consistent with disease in humans and nonhuman primates and included early infection of macrophages and dendritiform cells, apoptosis of bystander lymphocytes, and increases in levels of proinflammatory cytokines. Most importantly, dysregulation of circulating levels of fibrinogen, protein C activity, and antifibrinolytic proteins and deposition of fibrin in tissues demonstrated both biochemical and microscopic evidence of disseminated intravascular coagulation.
  
  
  CONCLUSIONS
  These findings suggest that the outbred guinea pig model recapitulates ZEBOV infection of primates better than inbred rodent models, is useful for dissecting key events in the pathogenesis of ZEBOV, and is useful for evaluating candidate interventions prior to assessment in primates.
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Cross
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Karla A
authors.initials: KA
authors.lastname: Fenton
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Joan B
authors.initials: JB
authors.lastname: Geisbert
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Chad E
authors.initials: CE
authors.lastname: Mire
authors.affiliation: Department of Microbiology and Immunology Galveston National Laboratory, University of Texas Medical Branch at Galveston.
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Geisbert
mesh_terms: D000818:Animals; D001777:Blood Coagulation / Q000502:physiology; D002460:Cell Line; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism; D015023:Democratic Republic of the Congo; D004195:Disease Models, Animal; D018450:Disease Progression; D029043:Ebolavirus / Q000472:pathogenicity; D005260:Female; D005337:Fibrin / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D006168:Guinea Pigs / Q000378:metabolism / Q000821:virology*; D019142:Hemorrhagic Fever, Ebola / Q000378:metabolism / Q000473:pathology* / Q000821:virology*; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology / Q000821:virology; D011323:Primates / Q000378:metabolism / Q000821:virology; D011486:Protein C / Q000378:metabolism; D014709:Vero Cells
chemical_list: D016207:Cytokines; D011486:Protein C; D005337:Fibrin; D005340:Fibrinogen
keywords: Ebola; adaptation; animal model; filovirus; guinea pig; pathogenesis; permeability; therapeutics; vaccines; virulence