Modeling the Disease Course of Zaire ebolavirus Infection in the Outbred Guinea Pig

Robert Cross, Karla A. Fenton, Joan B. Geisbert, Chad Mire, Thomas Geisbert

Research output: Contribution to journalArticle

28 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)S305-S315
JournalJournal of Infectious Diseases
Volume212
DOIs
StatePublished - Oct 1 2015

Fingerprint

Ebolavirus
Democratic Republic of the Congo
Guinea Pigs
Primates
Ebola Hemorrhagic Fever
Infection
Rodentia
Antifibrinolytic Agents
Disseminated Intravascular Coagulation
Protein C
Fibrin
Fibrinogen
Macrophages
Lymphocytes
Apoptosis
Cytokines

Keywords

  • adaptation
  • animal model
  • Ebola
  • filovirus
  • Guinea pig
  • pathogenesis
  • permeability
  • therapeutics
  • vaccines
  • virulence

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Modeling the Disease Course of Zaire ebolavirus Infection in the Outbred Guinea Pig. / Cross, Robert; Fenton, Karla A.; Geisbert, Joan B.; Mire, Chad; Geisbert, Thomas.

In: Journal of Infectious Diseases, Vol. 212, 01.10.2015, p. S305-S315.

Research output: Contribution to journalArticle

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